Hindawi

Case Reports in Oncological Medicine

Volume 2023, Article ID 9647892, 6 pages
https://doi.org/10.1155/2023/9647892

Case Report
Malignant Melanoma Presenting as Spinal Cord and
Pleural Lesions

Aysha Albastaki ,1 Sharifa Ahmed,1 Asher Khan,2 Abeer Farhan,1 and Talal Almayman1
1
King Hamad University Hospital, Al Muharraq, Bahrain
2
Royal College of Surgeons-Medical University of Bahrain, Al Muharraq, Bahrain

Correspondence should be addressed to Aysha Albastaki; aysha.a97@hotmail.com

Received 9 September 2022; Revised 28 January 2023; Accepted 1 February 2023; Published 21 February 2023

Academic Editor: Satish Gandhesiri

Copyright © 2023 Aysha Albastaki et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.

Primary spinal cord melanoma (PSCM) and primary pleural melanoma (PPM) are extremely rare entities with scarce cases
reported in the literature. We present a case of a 54-year-old male diagnosed with possible primary pleural melanoma and
primary spinal melanoma, managed with partial surgical resection, postoperative radiotherapy, and chemotherapy consisting of
Ipilimumab, nivolumab, and temozolomide. This leads to decreased symptoms and improved quality of life of the patient. In
this case report, we review the literature on PSCM and PPM in detail, addressing the pertinent clinical aspects as well as
current and upcoming therapeutic options.

1. Introduction stant, and progressively worsening. No other associated symp-

Malignant melanoma (MM) is the most aggressive form of
skin cancer. In the recent years, major advances in diagnos-
tic and therapeutic research have increased our understand-
ing of malignant melanoma and led to the identification of
new therapeutic targets and strategies, improving the prog-
nosis of affected patients. [1] The most common origin for
primary MM is the skin which accounts for 91.2% of all
reported cases of primary MM [2]. Other primary sites for
melanoma are relatively uncommon. Primary spinal cord
and primary pleural melanomas are extremely rare malig-
nancies, with only 9 reported cases of primary pleural mela-
nomas in the literature and a relatively small number of
cases of primary spinal cord melanomas [3, 4]. To the best
of our knowledge, this is the first case of a melanoma pre-
senting as a spinal cord and pleural lesion.
2. Case Presentation
A 54-year-old male patient presented to the emergency
department with a two-month history of neck and back pain.
The back pain was localized to the interscapular region, con-
toms were present such as upper and lower limb weakness or
numbness, headaches, changes in vision, hearing, or taste, or
changes in urinary or bowel habits. System review was other-
wise negative. The patient did not have a history of similar
symptoms. The patient was a known case of type 2 diabetes
mellitus and has been well controlled on insulin and metfor-
min (500 mg BD) for the last 10 years. The remainder of the
patient’s medical history was unremarkable; the patient works
in an office job, has no history of malignancy in the family, and
does not smoke nor drink alcohol.
On the 26th of January 2019, the patient went to a private
clinic where an MRI of his dorsal spine revealed a large expan-
sile lesion seen in the posterior element of the T5 vertebrae,
involving both laminae, spinous processes, the facet joints,
both pedicles, and the transverse processes. The lesion mea-
sured 2:5 × 4 × 3:2 cm in the anteroposterior (AP), transverse,
and longitudinal axes, respectively. There was resorption of
the spinal canal cortical outline, and the lesion was signifi-
cantly encroaching upon the spinal canal, causing significant
spinal cord compression. At the site of maximal compression,
the spinal canal measured 3 mm compared to 1.5 cm at the T4
level superiorly. On T2-weighted MRI, the signal intensity of
2 Case Reports in Oncological Medicine
this lesion was heterogenous with a bright thick signal on the
outer aspect of the lesion and low central signal intensity
(Figure 1). On T1-weighted MRI, the signal intensity was
inversed, brighter in the central part of the lesion and darker
on the periphery. There is only minimal post-contrast
enhancement which was mainly peripheral. Another well-
defined, round lesion was noted on the right side at the T3-4
level, located retropleural, and paravertebral. The lesion had
similar signal characteristics as the spinal lesion, along with
areas of calcifications on contrast-enhanced CT. The lesion
measured 3:7 × 3:4 × 3:4 cm in the AP, transverse, and longi-
tudinal axes, respectively (Figure 2). Despite abutting on the
right vertebral wall, there were no signal abnormalities on
PET-CT within the vertebral body or adjacent bony structures.
There was also no obvious intrathoracic infiltration. Thus, this
lesion likely originates from the pleura.
3. Examination
On physical examination of the patient, there were no obvi-
ous structural deformities, the patient displayed a full range
of motion in both the thoracic and lumbar spine, and the
neurological examination of both upper and lower limbs
was completely normal.
One day after admission, a contrast-enhanced computed
tomography (CT) scan of the thoracic spine was conducted
at our institution which confirmed the findings. Due to the
compression of the spinal cord, the patient underwent an
urgent decompressive laminectomy and resection of the
dura followed by excision of the posterior column tumor at
the T4-6 region under general anaesthesia on the 29th of
January 2019. Intraoperatively, a highly vascular black mass
was seen which was then debulked.
On the 5th of February 2019, the patient’s histological
report showed a malignant cellular neoplasm composed of
sheets, nests, and clusters of pleomorphic malignant cells with
hyperchromatic nuclei, prominent nucleoli, and eosinophilic
to scanty cytoplasm. Moreover, abnormal pigment deposition,
melanin, was seen in most of the cells. The tumor was positive
for Melan-A, HMB-45, and S-100, as well as a positive Ki-67
expression of 96%, thus confirming the diagnosis of mela-
noma. The patient was discharged on the same day and
received follow-up from neurosurgery, thoracic surgery,
oncology, and endocrinology in the outpatient clinic. The
patient had a full physical examination by ophthalmology,
otolaryngology, and dermatology for any evidence of primary
lesions on the skin, mucosa, or nails. No lesions were found.
The patient was seen in the endocrinology clinic where it
was observed that his fasting blood glucose level was well con-
trolled, and he was discharged on only oral metformin with a
dose of 500 mg twice daily.
On the 11th of February 2019, a positron emission
tomography-computed tomography (PET-CT) scan was con-
ducted and showed that the mass at the T3-4 region was fluo-
rodeoxyglucose (FDG) avid, with a maximum standardized
uptake value (SUVmax) of 5.4. No other hypermetabolic
lesions were detected in the rest of the surveyed body. Follow-
ing surgery, the patient received palliative radiotherapy to the
dorsal spine. The patient’s management was continued using 9
Figure 1: T2-weighted sagittal MR of the neck showing the spinal
lesion at the level of T5.
cycles of nivolumab. Unfortunately, follow-up imaging on the
15th of July 2019 showed the development of a new metaboli-
cally active metastatic lesion in the right middle pulmonary
lobe and left lower paracardiac lung lobe, and progression of
the size and metabolic activity of the lesions denoting lung
metastasis (Figures 3 and 4). Thus, the patient was started in
ipilimumab in addition to nivolumab. The thoracic team was
consulted and decided that total resection is not deemed feasi-
ble due to intraspinal extension of the primary lesion as well as
multiple lung metastases.
Further follow-up imaging showed progression of the
spinal lesion as well as lung nodules. Since then, the patient
has been started on temozolomide. He completed 10 cycles of
temozolomide at a dose of 270 mg once daily for 5 continuous
days. During follow-up, imaging revealed metabolic regression
of the spinal lesion as well as the pulmonary nodules. Clinically,
he became symptomatically well with significant improvement
of the back pain that he now describes as mild, intermittent,
and adequately managed with paracetamol. As a result of this,
the patient has been able to return to work.
4. Discussion
Malignant melanoma is considered the most fatal form of
skin cancer. It represents less than 5% of all cutaneous
malignancies, while accounting for the majority of skin can-
cer deaths [5, 6]. Most commonly, malignant melanoma is
present on the skin, and lesions discovered in other organs
such as the CNS and the pleura are secondary to metastasis.
PSCM are an even rarer occurrence, accounting for approx-
imately 1% of melanoma cases [7–9] or 0.005 cases per
100,000 [10]. The peak incidence is in the fifth decade of life,
with no apparent predilection towards the male or female
sex [7]. PSM are located either intradurally or extradurally
and may possess intra- or extramural components [11]. A
Case Reports in Oncological Medicine
Figure 2: T2-weighted sagittal (view/section) MRI of the neck
showing the pleural lesion.
Figure 3: High-resolution chest CT shows a pulmonary nodule in
the right middle lung lobe denoting pulmonary metastasis.
Figure 4: High-resolution chest CT showing another left lower lung
lobe paracardiac lung mass denoting another metastatic lesion.
3
review of 60 cases of PSM by Li et al. [12] showed that 62.4%
were extramedullary while 37.7% were intramedullary.
There are also reports of multifocal primary cervical spinal
cord melanomas. With regard to the distribution along the
spinal cord, the lesions are most located in the thoracic, cer-
vical, and lumbar regions respectively [12–15].
4.1. Clinical Presentation of Spinal and Pleural Melanomas.
Multiple reports of CNS melanoma in the literature have
shown different clinical presentations including symptoms of
myelopathy, dysesthesia, weakness, pain, and fecal and urinary
incontinence [13, 15–17]. Hydrocephalus has also been
reported as spinal cord lesions that can disturb the cerebrospi-
nal fluid circulation [18]. In the case of pleural melanomas, the
main symptoms include dyspnea, chest pain, and cough [3].
4.2. The Origin of Primary Pleural and Spinal Cord Melanomas.
Primary CNS melanomas may arise from either neuroectoder-
mal rest cells or leptomeningeal melanoblasts, which originate
from the neural crest [7–9, 19]. A hypothesis for development
of primary melanoma suggests that a few neural crest cells do
not migrate during embryogenesis and stay within the neural
tube [20]. These cells fail to establish the signaling pathways
required to normally differentiate and mature. Moreover, sev-
eral hypotheses have been proposed regarding the development
of a primary melanoma from areas devoid of melanocytes, such
as in the pleura. Hypotheses include growth from pigment blast
cells, growth from multipotent stem cells, squamous metapla-
sia, growth from aberrant skin nevus cells which transfer along
the lymphatic pathway, or, alternatively, disappearance of the
primary tumor after metastasis [21].
4.3. Diagnosis of Spinal and Pleural Melanomas. Early and cor-
rect diagnosis is the key for ensuring the best clinical outcome.
MRI remains the gold standard for diagnosing spinal and
pleural melanomas. Characteristic features on MRI include
hyperintensity on T1-weighted sequencing, hypointensity or
isointensity on T2-weighted sequences, and homogenous
enhancement with gadolinium contrast agents [7, 15, 22].
The paramagnetic properties of melanin or hemorrhagic ele-
ments in the tumors are reported to be the reason behind these
signal intensity features [7]. Therefore, MRI findings vary
depending on the number of melanin-containing cells and
the presence or absence of hemorrhage [14]. These character-
istics are similar to other tumors of melanocytic origin.
Although MRI imaging aids in the diagnosis, it does not differ-
entiate between primary melanoma and other malignant
lesions. This can be done by exclusion of primary lesions via
evaluation by ophthalmology, otolaryngology, and dermatol-
ogy. CT findings include a hyperdense appearance of the
lesion when enhanced by intravenous contrast [23].
The definitive diagnosis of melanoma can only be made by
histopathological examination of an excisional biopsy [24].
Histopathological features include spindle or epithelioid cells
arranged in sheets, nests, or whorls with well-differentiated
melanocytes and melanin-rich cytoplasm [25]. Markers on
immunohistochemistry include HMB-45 and S-100. Moreover,
as molecular mechanisms are better understood, researchers
and clinicians have been able to utilize molecular biomarkers
4 Case Reports in Oncological Medicine
and immunohistochemistry in the interpretation of difficult
cases [26]. Immunohistochemistry is now the most commonly
used technique by pathologists to diagnose melanoma and is
reliable, inexpensive, and relatively available. Some of the mela-
nocytic biomarkers with highest specificity include Melan-A,
MART-1, and HMB-45, the expression of which is mostly lim-
ited to melanocytic tumors. The most commonly used prolifer-
ation marker is Ki-67 which is elevated in most highly
aggressive melanomas, such as in our patient [26].
Upon histopathological diagnosis, the next step is to deter-
mine if the lesion is primary or metastatic. This is done by a
thorough and complete examination of the skin, including
inspection of the mucosa and genitalia. Moreover, ophthalmo-
logical (including retinal) and gastrointestinal examination is
also necessary [7, 27]. PET-CT following FDG injection is
accurate in detecting additional foci of disease [9, 27]. The
FDG PET-CT can show the difference between malignant
and benign tumors, where the pleural malignant tumor may
show focal or diffuse increased FDG uptake with standardized
uptake values (SUV) of 10 or greater. However, the increase of
FDG uptake is mild and in pleural benign diseases with SUV
approximately equal to 1. FDG may be also used to help local-
ize the site for biopsy and improve accuracy [3].
It is difficult to differentiate between various melanin-
containing tumors intraoperatively; however, features such
as dural mater attachment and a distinct dark black color
may indicate that the tumor originates from leptomeningeal
melanocytes [12]. However, surgeons need to keep in mind
that spinal meningiomas may mimic this appearance when
complicated by hemorrhage [12].
4.4. Staging. Aside from the Clark and Breslow’s depth used
to stage cutaneous melanoma, the American Joint Commit-
tee on Cancer (AJCC) proposed the TNM (tumor, node, and
metastasis) staging system. It provides a guideline for staging
a patient by combining the histological attributes of the pri-
mary tumor (T), the presence and extent of regional lymph
node disease (N), and the presence and extent of metastases
(M). The guideline was most recently revised in 2018 [28].
4.5. Medical and Surgical Management. The management of
melanoma is a complex and continually evolving subject. Plas-
tic surgeons, dermatologists, oncologists, surgical oncologists,
and neurosurgeons must keep up to date with recent changes
in the field. There have been several new and innovative drugs
developed over the last 10 years that have greatly improved the
prognosis for patients with metastatic melanoma secondary to
the identification of new biomarkers and drug targets. For stage
IV (or metastatic) melanoma, the National Comprehensive
Cancer Network recommends Ipilimumab (IgG1 anti-CTLA-
4 antibodies), vemurafenib (BRAF inhibitors specific to mela-
noma harboring the BRAF V600E and V600E/K mutations),
dabrafenib, and high-dose interleukin-2 as first-line agents.
Moreover, other newly emerging therapies include the anti-
programmed cell death 1 receptor agents (nivolumab and pem-
brolizumab) and oncolytic vaccines. The most well-known of
the immunotherapies targeted against cytotoxic T
lymphocyte-associated antigen 4 (CTLA-4) and programmed
cell death protein 1 (PD-1) have become the frontline treat-
ment of metastatic melanoma in many clinical scenarios [29].
Ipilimumab, which was used in our case, has (been shown to
be beneficial) shown benefit in patients with metastatic mela-
noma in multiple clinical trials. Moreover, a phase 3 clinical
trial is currently ongoing/underway comparing nivolumab,
ipilimumab, and a combination of the two (NCT01844505).
Combination therapies involving the use of multiple immune
modulating agents show great promise and may be common-
place in future treatment plans [30].
For spinal cord melanomas, complete surgical resection
is the treatment of choice [7, 15, 31]. However, some reports
show long-term survival even with subtotal resection [14].
Additionally, adjuvant radiotherapy is recommended in all
cases [7, 15, 16, 31]. In literature, the dose of radiation
administered ranged between 30 and 60 Gy, with the mean
total dose found to be 47 Gy [14]. The use of chemotherapy
also seems to be promising especially in cases with incom-
plete resection [14, 31]. Studies have shown that temozolo-
mide, as used in our patient, although costlier than other
chemotherapeutic agents, is well tolerated and has the bene-
fit of the additional advantage of improving the quality of
life of patients with metastatic melanoma [32, 33].
A meta-analysis showed that chemotherapy and biological
therapy were capable of reducing the recurrence rate and
increasing survival (rates) only by 3% after five years [12, 34].
Although immunotherapy is the current focus of inter-
est, there is no literature available regarding the use of
immunotherapy in PSCM or PPM.
4.6. Follow-Up and Surveillance. Surveillance imaging every 6
months is supported by very limited data, and some patients
with high-risk and aggressive disease require more frequent
imaging (for instance, every 3 months). Yet, serial imaging is
recommended at regular intervals even after complete surgical
resection [19]. Moreover, follow-up of patients with mela-
noma, regardless of radiological surveillance, should include
regular routine clinical examinations as well as a full skin
examination and palpation of nodal basins [35].
4.7. Prognosis. Primary CNS melanoma has a much better
prognosis compared to metastatic CNS melanoma (which
has median survival between 3 to 6 months) [11, 14, 31]. A
proposed explanation (for this) is due to the lack of lym-
phatic vessels in the CNS, limiting potential for metastasis
[14]. The clinical course and survival are unpredictable of
primary CNS melanoma, with some cases reporting several
years of survival [15], whereas others reporting months
[14]. Larson et al. reported an average life expectancy of
approximately 7 years after surgery with radiotherapy [17].
In a review done by Kim et al. [14], the mean duration of
survival was 28.8 months and with a range of 3 months to
13 years. In one case report, the progression of the tumor
was controlled for 21 years. This may have been due to radi-
ation therapy as well as the intrathecal injection of interferon
beta [36]. Metastasis was observed in patients after surgery,
and sites of metastases include the brain, lung, bone, and
other systemic metastases [11, 37, 38].
Case Reports in Oncological Medicine
5. Conclusion
In summary, we report a rare case of metastatic malignant
melanoma presenting as a spinal and pleural lesion. The case
highlights the rarity of such presentation. We review the
available literature on this rare presentation and the recom-
mended available medical and surgical treatments, as well as
upcoming therapeutic options.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
References
[1] S. N. Markovic, L. A. Erickson, T. J. Flotte et al., “Metastatic
malignant melanoma,” Giornale Italiano di Dermatologia e
Venereologia, vol. 144, no. 1, pp. 1–26, 2009.
[2] A. E. Chang, L. H. Karnell, and H. R. Menck, “The National
Cancer Data Base report on cutaneous and noncutaneous mel-
anoma: a summary of 84,836 cases from the past decade. The
American College of Surgeons Commission on Cancer and
the American Cancer Society,” Cancer, vol. 83, no. 8,
pp. 1664–1678, 1998.
[3] K. Murakami, K. Tobino, Y. Yamaji et al., “Primary pleural
melanoma: a case report and literature review,” Internal Med-
icine, vol. 58, no. 22, pp. 3273–3276, 2019.
[4] E. Perera, N. Gnaneswaran, R. Jennens, and R. Sinclair,
“Malignant melanoma,” Healthcare, vol. 2, no. 1, pp. 1–19,
2014.
[5] E. Linos, S. M. Swetter, M. G. Cockburn, G. A. Colditz, and
C. A. Clarke, “Increasing burden of melanoma in the United
States,” The Journal of Investigative Dermatology, vol. 129,
no. 7, pp. 1666–1674, 2009.
[6] N. Howlader, A. M. Noone, M. Krapcho et al., “SEER cancer
statistics review, 1975-2012,” National Cancer Institute. 2014,
http://seer.cancer.gov/archive/csr/1975_2012/.
[7] D. Farrokh, P. Fransen, and D. Faverly, “MR findings of a pri-
mary intramedullary malignant melanoma: case report and lit-
erature review,” AJNR. American Journal of Neuroradiology,
vol. 22, no. 10, pp. 1864–1866, 2001.
[8] E. Pappenheim and S. K. Bhattacharji, “Primary melanoma of
the central nervous system,” Archives of Neurology, vol. 7,
no. 2, pp. 101–113, 1962.
[9] N. K. Lee, B. H. Lee, Y. J. Hwang et al., “Findings from CT,
MRI, and PET/CT of a primary malignant melanoma arising
in a spinal nerve root,” European Spine Journal, vol. 19, Sup-
plement 2, pp. S174–S178, 2010.
[10] G. K. Kounin, K. V. Romansky, L. D. Traykov, P. M. Shotekov,
and D. Z. Stoilova, “Primary spinal melanoma with bilateral
papilledema,” Clinical Neurology and Neurosurgery, vol. 107,
no. 6, pp. 525–527, 2005.
[11] O. Ganiusmen, F. D. Ozer, M. Mete, N. Ozdemir, and
U. Bayol, “Slow progression and benign course of a primary
malign melanoma of a lumbar nerve root,” Clinical Neurology
and Neurosurgery, vol. 114, no. 2, pp. 166–168, 2012.
[12] Y. P. Li, H. Z. Zhang, L. She et al., “Primary extramedullary
spinal melanoma mimicking spinal meningioma: a case report
and literature review,” Oncology Letters, vol. 8, no. 1, pp. 339–
344, 2014.
5
[13] A. D. Fuld, M. E. Speck, B. T. Harris et al., “Primary melanoma
of the spinal cord: a case report, molecular footprint, and
review of the literature,” Journal of Clinical Oncology, vol. 29,
no. 17, pp. e499–e502, 2011.
[14] M. S. Kim, D. H. Yoon, and D. A. Shin, “Primary spinal cord
melanoma,” Journal of Korean Neurosurgical Association,
vol. 48, no. 2, pp. 157–161, 2010.
[15] M. Wuerdeman, S. Douglass, R. B. Abda, and M. Krasnokutsky,
“A rare case of primary spinal cord melanoma,” Radiology Case
Reports, vol. 13, no. 2, pp. 424–426, 2018.
[16] K. Salame, O. Merimsky, J. Yosipov, I. Reider-Groswasser,
S. Chaitchik, and G. E. Ouaknine, “Primary intramedullary
spinal melanoma: diagnostic and treatment problems,” Jour-
nal of Neuro-Oncology, vol. 36, no. 1, pp. 79–83, 1998.
[17] T. C. Larson 3rd, O. W. Houser, B. M. Onofrio, and D. G. Piep-
gras, “Primary spinal melanoma,” Journal of Neurosurgery,
vol. 66, no. 1, pp. 47–49, 1987.
[18] D. H. Jeong, C. K. Lee, N. K. You, S. H. Kim, and K. H. Cho,
“Primary spinal cord melanoma in thoracic spine with lepto-
meningeal dissemination and presenting hydrocephalus,”
Brain Tumor Research and Treatment, vol. 1, no. 2, pp. 116–
120, 2013.
[19] T. Yamasaki, H. Kikuchi, J. Yamashita, R. Asato, and M. Fujita,
“Primary spinal intramedullary malignant melanoma: case
report,” Neurosurgery, vol. 25, no. 1, pp. 117–121, 1989.
[20] F. M. Salpietro, C. Alafaci, O. Gervasio et al., “Primary cervical
melanoma with brain metastases,” Journal of Neurosurgery,
vol. 89, no. 4, pp. 659–666, 1998.
[21] S. W. Um, C. G. Yoo, C. T. Lee, S. K. Han, Y. S. Shim, and
Y. W. Kim, “Apparent primary pleural melanoma: case report
and literature review,” Respiratory Medicine, vol. 97, no. 5,
pp. 586-587, 2003.
[22] T. Wadasadawala, S. Trivedi, T. Gupta, S. Epari, and R. Jalali,
“The diagnostic dilemma of primary central nervous system
melanoma,” Journal of Clinical Neuroscience, vol. 17, no. 8,
pp. 1014–1017, 2010.
[23] K. Fujimori, K. Sakai, F. Higashiyama, F. Oya, T. Maejima, and
T. Miyake, “Primary central nervous system malignant mela-
noma with leptomeningeal melanomatosis: a case report and
review of the literature,” Neurosurgical Review, vol. 41, no. 1,
pp. 333–339, 2018.
[24] S. N. Pavri, J. Clune, S. Ariyan, and D. Narayan, “Malignant
melanoma: beyond the basics,” Plastic and Reconstructive Sur-
gery, vol. 138, no. 2, pp. 330e–340e, 2016.
[25] D. J. Brat, C. Giannini, B. W. Scheithauer, and P. C. Burger,
“Primary melanocytic neoplasms of the central nervous sys-
tem,” The American Journal of Surgical Pathology, vol. 23,
no. 7, pp. 745–754, 1999.
[26] R. H. Kim and S. A. Meehan, “Immunostain use in the diagno-
sis of melanomas referred to a tertiary medical center: a 15-
year retrospective review (2001–2015),” Journal of Cutaneous
Pathology, vol. 44, no. 3, pp. 221–227, 2017.
[27] F. Tuz Zahra, Z. Ajmal, J. Qian, and S. Wrzesinski, “Primary
intramedullary spinal melanoma: a rare disease of the spinal
cord,” Cureus, vol. 13, no. 7, article e16194, 2021.
[28] P. Gerami, K. Busam, A. Cochran et al., “Histomorphologic
assessment and interobserver diagnostic reproducibility of
atypical spitzoid melanocytic neoplasms with long-term fol-
low-up,” The American Journal of Surgical Pathology, vol. 38,
no. 7, pp. 934–940, 2014.
6 Case Reports in Oncological Medicine

[29] B. Herzberg and D. E. Fisher, “Metastatic melanoma and

immunotherapy,” Clinical Immunology, vol. 172, pp. 105–
110, 2016.
[30] E. Maverakis, L. A. Cornelius, G. M. Bowen et al., “Metastatic
melanoma - a review of current and future treatment options,”
Acta Dermato-Venereologica, vol. 95, no. 5, pp. 516–524, 2015.
[31] S. V. Liubinas, N. Maartens, and K. J. Drummond, “Primary
melanocytic neoplasms of the central nervous system,” Journal
of Clinical Neuroscience, vol. 17, no. 10, pp. 1227–1232, 2010.
[32] R. H. Li, X. Y. Hou, C. S. Yang et al., “Temozolomide for treat-
ing malignant melanoma,” Journal of the College of Physicians
and Surgeons–Pakistan, vol. 25, no. 9, pp. 680–688, 2015.
[33] S. Mallick, S. Roy, N. P. Joshi, and P. K. Julka, “Primary spinal
melanoma treated with adjuvant radiotherapy and concurrent
temozolomide: a case report and review of literature,” Journal
of Cancer Research and Therapeutics, vol. 11, no. 4, p. 1027,
2015.
[34] K. Wheatley, N. Ives, A. Eggermont et al., “Interferon-α as
adjuvant therapy for melanoma: an individual patient data
meta-analysis of randomised trials,” Journal of Clinical Oncol-
ogy, vol. 25, Supplement 18, pp. 8526–8526, 2007.
[35] M. D. Howard, “Melanoma radiological surveillance: a review
of current evidence and clinical challenges,” The Yale Journal
of Biology and Medicine, vol. 93, no. 1, pp. 207–213, 2020.
[36] M. Nishihara, T. Sasayama, T. Kondoh, K. Tanaka,
E. Kohmura, and H. Kudo, “Long-term survival after surgical
resection of primary spinal malignant melanoma,” Neurologia
Medico-Chirurgica (Tokyo), vol. 49, no. 11, pp. 546–548, 2009.
[37] Q. Y. Liu, A. M. Liu, H. G. Li, and Y. B. Guan, “Primary spinal
melanoma of extramedullary origin: a report of three cases and
systematic review of the literature,” Spinal Cord Series And
Cases, vol. 1, no. 1, p. 15003, 2015.
[38] J. Yu, D. D. Zhao, S. Chen, J. M. Zhang, and J. Xu, “Primary
melanoma of the cervical spine with cerebral metastases: case
report and review of the literature,” The Journal of Interna-
tional Medical Research, vol. 40, no. 3, pp. 1207–1215, 2012.
 Clinical Neurology and Neurosurgery 205 (2021) 106649

Contents lists available at ScienceDirect

Clinical Neurology and Neurosurgery

journal homepage: www.elsevier.com/locate/clineuro

Primary Spinal Melanoma: Case Report and Systematic Review

Erika Haberfellner a, Mohammad Elbaroody b, Abdullah F. Alkhamees a, c, Abdelfatah Alaosta a, d,
Sydney Eaton a, Elise Quint a, Saba Shahab a, Avalon O’Connor a, Jacob Im a, Asham Khan e,
Yasser El-Gohary f, Mohamed Lotfy b, Mohamed Sawan b, Abdalla Shamisa g, Mohamed A.
R. Soliman a, b, 1, *
a
Schulich School of Medicine and Dentistry, Western University, Ontario, Canada
b
Neurosurgery Department, Cairo University, Egypt
c
Neurosurgery Department, Qassim University, Kingdom of Saudi Arabia
d
Neurosurgery Department, Sirte University, Libya
e
Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, United States
f
Pathology Department, Windsor Regional Hospital, Western University, Canada
g
Neurosurgery Department, Windsor Regional Hospital, Western University, Canada

A R T I C L E I N F O A B S T R A C T

Keywords: Introduction: Primary malignant melanoma of the spinal cord (PSM) is a rare condition with limited evidence
Primary spinal melanoma regarding its diagnosis (clinical and radiographic), management, and prognosis. Our aim was to report an
Adjuvant therapy extremely rare two cases of primary malignant melanoma of the spine one of them is sacral melanoma which
Sacral
represents the second reported case in the literature and to conduct a systematic review of the relevant literature.
Intramedullary
Extramedullary
Methods: The diagnosis and management of these cases were retrospectively reviewed. Using the PRISMA
guideline, we conducted a systematic review of the literature to analyze different management strategies and the
prognosis of such pathology.
Results: All two patients were operated on, and received gross total removal of their tumors, with extended follow
up for tumor recurrences. One of the cases involved a sacral tumor, which was resected without adjuvant
therapy. The other one was seen by oncology and received post-operative chemo- and radio- therapy. In addition
to the aforementioned cases, we present a comprehensive review of the literature on PSM from 1950 to the
present, demonstrating that PSM is a very rare tumor, with a limited counted number of cases reported
worldwide.
Conclusion: In conclusion, we report an exceedingly rare two cases of primary malignant melanoma of the spine.
Early surgical intervention is key to the management of these rare and aggressive tumors. GTR should be
attempted if possible.

1. Introduction
Primary Spinal Melanoma (PSM) is a rare primary malignancy ac­
counting for less than 1% of all CNS melanomas [1]. Malignant mela­
noma as a whole, however, is on the rise and thus spinal surgeons must
be able to appropriately diagnose and treat these uncommon spinal le­
sions [2]. There are few published cases of PSM, and therefore limited
evidence exists regarding the diagnosis, management and prognosis of
these tumors. We report an extremely rare two cases of primary malig­
nant melanoma of the spine. Our case of PSM of the sacral area will be
the second published case of sacral PSM in the English literature [3].
Additionally, we completed a comprehensive review of the English
literature on PSM in order to analyze the clinical, radiological and his­
tological findings seen with these tumors, as well as the treatment
methods most commonly and successfully utilized. Based on our find­
ings, we developed an algorithm to aid clinicians in the diagnosis and
management of PSM. The two patients in our study were informed that
data from their medical records would be published and were consented.

* Corresponding author at: Schulich School of Medicine and Dentistry, Western University, Ontario, Canada.
E-mail address: moh.ar.sol@kasralainy.edu.eg (M.A.R. Soliman).
1
ORCID: 0000–0003-1855–2551

https://doi.org/10.1016/j.clineuro.2021.106649
Received 2 February 2021; Received in revised form 15 March 2021; Accepted 10 April 2021
Available online 17 April 2021
0303-8467/© 2021 Elsevier B.V. All rights reserved.
E. Haberfellner et al. Clinical Neurology and Neurosurgery 205 (2021) 106649

Nomenclature MITF Microphthalmia-associated transcription factor

MRI Magnetic Resonance Imaging
C Cervical NOS Not otherwise specified
CARE case reports NS Not stated
Cm Centimeter NTR Near total resection
CNS Central nervous system OR Operating room
CT Computerized Tomography PRISMA preferred reporting items for systematic reviews and meta-
DDx Differential Diagnosis analyses
F Female PSM Primary spinal melanoma
GI gastrointestinal R Radiation adsorbed dose
GTR Gross total resection S Sacral
Gy Gray STR Subtotal resection
IV Intravenous T Thoracic
L Lumbar T1W T1 weighted images
M Male T2W T2 weighted images
MART-1 Melanoma antigen recognized by T cells Tx Treatment
Mets Metastasis

Fig. 1. PRISMA flow diagram illustrating article selection process.

2
E. Haberfellner et al.
2. Case report
We reported our cases according to case reports (CARE) and
preferred reporting items for systematic reviews and meta-analyses
(PRISMA) guidelines (Fig. 1) [4,5].
2.1. Case 1
A 62-year-old male experienced 6 months of gradually worsening
low back pain (more severe at night), along with progressive lower limb
heaviness and urgency to micturition. Just prior to presentation he also
experienced one day of urinary and stool incontinence. Past medical
history was non-contributory. On examination, both lower limbs were
found to be hypotonic with motor power of grade 2/5 bilaterally. There
was also hyperreflexia of the patellar, ankle jerk, and plantar reflexes
with sustained clonus. Babinski reflex was positive bilaterally. The
sensory level was determined to be T12.
Imaging with MRI revealed a lesion spanning the T10–11 spinal
levels (Fig. 2). The tumor was slightly hyperintense on T1W and iso­
intense on T2W images and showed homogenous enhancement with IV
contrast administration. The absence of a primary tumor outside of the
spinal cord was confirmed with a full dermatological examination, a full
ophthalmological examination, and upper and lower gastrointestinal
(GI) endoscopy. CT of the head, chest, abdomen and pelvis was also done
to rule out any other primary tumors or metastases.
After the lesion was identified with imaging, the patient was taken to
the operating room (OR) for urgent decompression. A T10-T11 lam­
inectomy was performed. On gross inspection, the tumor was black and
well-demarcated. It was determined to be an intradural, extramedullary
lesion with invasion into the spinal cord (intramedullary-extra­
medullary). A Gross Total Resection (GTR) was performed. The
3
Clinical Neurology and Neurosurgery 205 (2021) 106649
pathological analysis confirmed malignant melanoma (Fig. 3). After
surgery, the patient’s motor power improved to grade 3/5, and they
were discharged to rehab. The patient was subsequently referred to the
cancer center, and radiotherapy was started (5 fractions of radiation
were given; the last treatment was administered 1-month post-
resection). 15 months after surgery, the patient is alive, has regained
his motor power and bowel and bladder function and has not had a
recurrence.
2.2. Case 2
A 29-year-old male experienced 2 months of severe low back pain,
right buttock and leg pain, and urinary urgency. Past medical history
was non-contributory. Examination revealed hypoesthesia along the
right S1-S2 dermatomes but was otherwise unremarkable. Deep tendon
reflexes were normal bilaterally, and sphincter tone and function
remained intact from the time of admission to the time of discharge.
MRI imaging reported an intradural extramedullary lesion spanning
the S1-S2 spinal levels and measuring 3.2 × 2.5 cm. The lesion was
hyperintense on both T1 and T2 weighted images and showed homog­
enous contrast enhancement (Fig. 4). The absence of any other primary
tumor was confirmed with an extensive work-up, including a full
dermatological examination, a bone-scan, tumor markers, upper and
lower GI endoscopy, and CT scan of the head, chest, abdomen and pelvis.
The patient was subsequently taken to the OR for surgery. A posterior
approach revealed a firm, dark, intradural mass, measuring
2.5 × 3.5 cm, with no infiltration of the nerve roots. A GTR was per­
formed, and clear planes of cleavage were noted between the mass and
the nerve roots. Pathological examination and immunohistochemical
analysis of the extracted tumor (which revealed strong tumor cell
immunoreactivity to the antibodies S-100 and HMB45) confirmed
Fig. 2. MRI Thoracic Spine with and
without contrast showing a T10–11
lesion; (A) T2-weighted image sagittal
views showing an isointense oval-shaped
intramedullary-extramedullary lesion
with surrounding spinal cord edema. (B)
T1-weighted image without contrast
sagittal views showing a hyperintense
oval-shaped intramedullary-extra­
medullary lesion. (C, D, and G) T1-
weighted image with contrast sagittal
views showing an enhancement oval-
shaped intramedullary-extramedullary
lesion. (E and H) T1-weighted image
without contrast axial views showing a
slightly hyperintense lesion. (F and I) T1-
weighted image with contrast axial views
showing an enhancing intramedullary-
extramedullary lesion.
E. Haberfellner et al.
Fig. 3. Pathology. (A) Cytology shows atypical cells. (B) H&E staining – note the atypical cells and pigment depositions. (C) Positive cytoplasmic immunostaining
Melan A (MART-1). (D) Positive nuclear stain MITF.
primary malignant melanoma.
The patient’s recovery from surgery was uncomplicated, and there
were no postoperative neurological deficits. Immediate improvement of
the low-back and right-sided buttock/lower extremity pain was noted,
and postoperative MRI confirmed complete resection of the tumor
without residual. The patient was referred to an oncologist post-
operatively and received adjuvant external beam radiation therapy.
Follow-up MRI 2 years after surgery revealed no recurrence and no
metastasis.
3. Discussion
Melanocytes are pigment-producing cells derived from the neural
crest during early embryonic development that migrate to the skin,
mucous membranes, and central nervous system (CNS) [6]. Melanoma is
a neoplasm that arises when these melanocytes undergo malignant
transformation and can occur in any tissue in which they reside, with the
skin and mucosa being most common [7,8]. Primary CNS Melanoma,
including Primary Spinal Melanoma (PSM), likely arises from melano­
blasts (the precursor cells to melanocytes) located within the lep­
tomeninges [9,10]. While primary CNS melanomas represent only 1% of
all melanomas, PSM is even more rare, accounting for only a fraction of
these lesions [1]. The first case of PSM was reported by Hirschburg in
1906, and since that time there have been a limited number of reported
case studies, thus the exact incidence of this rare tumor remains un­
known [11].
We performed a systematic retrospective analysis of the English
literature on PSM published since 1950 on the PubMed Medline data­
base using the search term “Primary Spinal Melanoma” in all fields.
3.1. Demographics
A total of 66 patients with PSM (including our two case reports) have
been summarized in a detailed table (Table 1). Our literature review
indicates that PSM occurs in patients with a mean age of 51 ± 16.6 years
(range 15–82 years) and that these tumors are uncommon before the age
4
Clinical Neurology and Neurosurgery 205 (2021) 106649
of 30 (7 of 64 cases) [12–17]. Additionally, our review revealed no
significant difference between the number of males and females affected
(1:1 ratio), which is aligned with what has been previously reported in
the literature [18].
Regarding the location of these lesions, PSM can occur within any
area of the spine, however, it has been reported that these tumors most
commonly occur within the cervical and thoracic cord [19]. This is in
line with what we found in our literature review, with 74.2% of cases
analyzed occurring within those regions – 34.8% cervical and 39.4%
thoracic. Of note, only 1 case of PSM occurring entirely within the sacral
region has been previously reported [13]. Thus, our case (case 2) rep­
resents the second entirely sacral PSM ever described. Additionally,
these tumors can be either intradural, extradural, or have both intra- and
extradural components. Of the 62 patients reviewed for whom the
location of the tumor was clearly described, the majority (53.2%) were
found to have intradural-extramedullary lesions [3,11–13,15–17,
20–38]. In contrast, 35.5% of patients were found to have intra­
medullary lesions [1,18–33,39]. Only 11.3% of patients had lesions that
were entirely extradural [7,8,12,40–43]. We did not find any report of a
case that mentioned that the lesion was extramedullary with an invasion
into the spinal cord as our first case.
3.2. Diagnosis
Presenting symptoms of PSM are variable and typically non-specific,
but commonly include back pain and symptoms of asymmetric
myelopathy - a clinical presentation suggestive of progressive spinal
cord compression [6,8,20]. MRI is the primary imaging modality used in
the evaluation of spinal pathology, and the majority of PSMs present
with characteristic findings [34]. Most of these lesions show signal
hyperintensity on T1W images [1,7,11,16–19,23,28–38,40,42,44–51],
signal hypointensity [1,7,11,16–18,29,31,33,34,36,38,42,44,46–51],
hyperintensity [3,28,30,37,45,52], or rarely isointensity [19,32,52] on
T2W images, as well as mild to moderate homogenous enhancement
after IV contrast administration [1,3,7,11,16–19,24,28,29,33–38,40,
45–50,52–54]. However, it is important to note that the MRI signal
E. Haberfellner et al. Clinical Neurology and Neurosurgery 205 (2021) 106649

Fig. 4. MRI Lumbosacral Spine without contrast showing an S1–2 lesion; (A) T2-weighted image sagittal views showing a hyperintense oval-shaped intradural
extramedullary lesion. (B) T1-weighted image with contrast sagittal views showing a homogenously enhanced oval-shaped intradural extramedullary lesion. (C) T1-
weighted image with contrast axial views showing a homogenously enhanced intradural extramedullary lesion.

produced by melanocytic tumors varies considerably depending on the
amount of melanin-containing cells within the lesion, with higher tumor
melanin concentrations associated with higher signal intensity on T1W
images and lower signal intensity on T2W images [55,56]. As well, the
presence or absence of acute or chronic intradural hemorrhages and fat
deposits has been shown to affect MRI appearance, with intratumoral
hemorrhage typically producing a heterogeneous signal on both T1W
and T2W images [34,40]. Therefore, the diagnosis of PSM may be sus­
pected based on imaging findings but cannot be confirmed with MRI
alone.
The diagnostic criteria for primary CNS melanoma were originally
described by Hayward [57]. According to this classification system, the
diagnosis is based on the absence of a primary tumor outside of the CNS
or in other CNS locations, and histopathological confirmation of mela­
noma [51,57]. While the great majority of melanocytic lesions arise
within the skin, other primary sites including the retinas and the GI tract
have been well-described [19]. Thus, the diagnosis of primary CNS
melanoma requires the absence of cutaneous, mucosal and ocular le­
sions. This is typically confirmed using a full dermatological examina­
tion, a retinal examination, upper and lower GI endoscopy, and CT scan
of the chest, abdomen, and pelvis [19,25]. As previously described, MRI
of the brain and spinal cord are generally used to identify the lesion of
interest and exclude any other CNS lesions [32,36]. Definitive
classification of tumor-type based on imaging alone, however, remains
impossible, as MRI findings with PSM are variable and may be similar to
those commonly observed in other tumors of the spine. For example,
meningiomas and pigmented schwannomas may contain melanin, and
subsequently produce signal hyper-intensity on T1W images [7,17,37,
38,46,52]. Thus these tumors, along with other pigmented CNS lesions
such as melanocytoma, pigmented medulloblastoma, ependymoma and
pineoblastoma, remain on the differential diagnosis after imaging [19,
31,45]. A definitive diagnosis of PSM therefore requires histopatholog­
ical confirmation, with melanomas identified based on their abundant
cytoplasmic pigment, infiltrative pattern, cellular and nuclear pleo­
morphism, and high mitotic rate with areas of necrosis [24,35,58]. In
addition to the pathological examination, immunohistochemical stain­
ing with HMB-45, S-100 or MelanA can help to confirm the diagnosis of
malignant melanoma [34]. Of the 50 cases reported after 1990, 45
(90%) included results of immunohistochemical staining with HMB-45,
S-100, and/or MelanA [1,3,8,11,14–17,19,23,24,28–37,40,42,44–52,
59].
Furthermore, while molecular analysis is often used to aid in the
management of advanced cutaneous melanomas [60], it has not been
commonly utilized for the diagnosis and management of PSM, with only
4 of the 66 cases reviewed (6.1%) reported genetic analysis of the tu­
mors [19,25,33,52]. Of note, PSM and metastatic melanoma seem to

5
 Table 1

E. Haberfellner et al.
Primary Spinal Melanoma: a review of the available English literature since 1950.
Authors Age Duration of Spinal T1W/T2W Extradural OR Pre-operative diagnosis Treatment Recurrence/metastases Follow-up
(year) (years) symptoms Level (s) /Enhancement on pre- Intradural
and sex operative MRI Extramedullary OR
Intradural
Intramedullary

Castaner et al. 52/F 12 months Lumbar NS Intradural- NS GTR NS Died a few days after
[20] intramedullary operation
Forbes et al. 57/M NS Thoraco- NS Intradural- NS T9-L1 Laminectomy Leptomeningeal dissemination 2 months, dead
[21] lumbar (2 intramedullary + adjuvant radiation
discrete (10x2500r)
masses)
King et al. 53/M 2 months T12-L1 NS Extradural NS STR Metastases to the dura mater 2 months, dead
[36] and brain base
Gibson et al. 51/F 22 months Thoracic NS Intradural- NS Laminectomy Leptomeningeal dissemination 1 month, dead
[22] (NOS) intramedullary
Hirano & 42/M 1 month T8-T10 NS Intradural- NS T7-T11 Laminectomy None 6.5 months, dead
Carton [27] intramedullary + adjuvant
radiotherapy (6000r
over 2 months)
Kiel et al. [59] 33/F 5 months C4-C6 NS Intradural- NS STR Cerebral mets + leptomeningeal 19 months, dead
extramedullary dissemination
Clifford et al. 64/M 4 months C4 NS Intradural- NS C3-C5 laminectomy Multiple cerebral and spinal 24 months, dead
[60] extramedullary metastases
Holaday et al. 20/F 3 months S2 NS Intradural- NS Laminectomy Local recurrence & widespread 12 months, dead
[13] extramedullary metastases
Ozden et al. 30/F NS T7-T10 NS Extradural NS T7-T10 laminectomy None 16 months, alive
[12] + adjuvant
chemotherapy
6

15/F NS C1-C6 NS Intradural- NS Cervical None 18 months, alive

extramedullary laminectomy
Larson et al. 73/M 6 months T6-T8 NS Intradural- NS STR+ adjuvant Leptomeningeal dissemination 84 months, alive
[23] intramedullary radiation (5000r)
63/M 96 months T9 NS Intradural- NS STR + adjuvant Local recurrence 156 months, dead
intramedullary radiation (6000r)
67/F 18 months T9-T11 NS Intradural- NS STR + adjuvant None Lost to follow-up
intramedullary radiation (4500r)
57/F 3 months C1-C3 NS Intradural- NS STR + adjuvant None 30 months, dead
intramedullary radiation (5000r)
69/F 24 months T9-T10 NS Intradural- NS STR None 45 months, dead
intramedullary

Clinical Neurology and Neurosurgery 205 (2021) 106649

Yamasaki et al. 31/M 6 months T6 NS Intradural – Intramedullary spinal STR + adjuvant None 23 months, alive
[28] intramedullary tumor (NOS) radiation (50 Gy over
5 weeks) + IFN
therapy
Salpietro et al. 62/M 1 month C3 T1W hyperintense/T2W Intradural – NS STR + adjuvant Metastases to the Brain 15 months, dead
[29] hyperintense/ intramedullary radiation (44 Gy over
enhancement 1 month)
Francois et al. 62/M 18 months T8 T1W hyperintense/ T2W Intradural- NS T7-T9 laminectomy None 28 months, alive
[29] hypointense/ intramedullary (GTR)
ehancement
Salame et al. 76/F 6 months T9-T10 T1W hyperintense/ Intradural- Intramedullary tumor T9-T11 laminectomy None 21 months, alive
[24] heterogeneous intramedullary with intra-tumoral + adjuvant radiation
enhancement bleeding (30 Gy in 8 fractions)
Brat et al. [14] 71/F NS T10 NS NS NS GTR None 14 months, alive
52/M NS C1 NS NS NS STR + adjuvant None 16 months, alive
radiation (40 Gy)
(continued on next page)
 Table 1 (continued )

E. Haberfellner et al.
Authors Age Duration of Spinal T1W/T2W Extradural OR Pre-operative diagnosis Treatment Recurrence/metastases Follow-up
(year) (years) symptoms Level (s) /Enhancement on pre- Intradural
and sex operative MRI Extramedullary OR
Intradural
Intramedullary

20/F NS C4 NS NS NS STR None 20 months, alive

57/F NS C4 NS NS NS STR + adjuvant None 8 months, dead
radiation (40 Gy)
Bidzinski et al. 36/M 8 months C6, C7 T1W hyperintense/ T2W Intradural- NS GTR + adjuvant None 4 years, alive
[31] hyperintense intramedullary radiation
Farrokh et al. 80/F NS T12-L1 T1W hyperintense/ T2W Intradural – NS STR No distant mets, but the tumor 9 months, alive
[1] hypointense/ moderate intramedullary was found to infiltrate the conus
homogeneous medularis and the nerve roots of
enhancement the cauda equina at the time or
surgery
Schneider & 65/M 6 months L5 moderate contrast Intradural- NS STR Dissemination to brain 1 month post-op,
Putzier [54] enhancement extramedullary (meningeal melanomatosis 2 dead
weeks post-op)
Sanz-Trelles 26/M 3 months L3 NS Intradural- NS GTR None 24 month, alive and
et al. [15] extramedullary asymptomatic
Freudenstein 54/F 8 years T10-T12 T1W hyperintense/T2W Intradural – Ependymoma STR + adjuvant 3.5 years after initial surgery 6 years, dead
et al. [32] hypointense extramedullary radiation + MRI revealed grow of the initial
chemotherapy tumor and new lesions at T5 and
T8; patient was treated with
intrathecal chemotherapy
65/M 2 years T10, T11 T1W hyperintense Intradural - Ependymoma STR (x2) + adjuvant Recurrence after 4 years 9 years, alive
intramedullary radiation (another STR done). Recurrence
again at 9 years
Kwon et al. 45/F 4 years, C6,C7 T1W hyperintense, T2W Extradural Complicated neurogenic GTR + adjuvant No recurrence or metastasis 8 months, alive
7

[37] worsening 5 hypointense tumor of the brachial radiation

months prior to plexus
presentation
Naing et al. 42/F NS L2 Enhancing lesion Intradural – NS STR + adjuvant No metastases or recurrence 7 years, alive
[25] intramedullary radiation + IFN
therapy
Kounin et al. 41/F 9 months C2-C4 T1W hyperintense/T2W Intradural- NS GTR NS 3 month, alive and
[44] hypointense/no extramedullary asymptomatic
enhancement
Unal & Castillo 37/F 4 months T7 T1W hyperintense/T2W Extradural NS GTR + No metastases, no recurrence 6 months alive
[35] heterogeneous chemotherapy
hypointensity/mild

Clinical Neurology and Neurosurgery 205 (2021) 106649

homogenous
enhancement
Kanatas et al. 76/F 8 months C6, C7 Homogenous Intradural – “mimicked” a STR + adjuvant None 6 months, alive
[53] enhancement extramedullary neurofibroma radiation
Kolasa et al. 57/F 2 months T10 T1W hyperintense/T2W Intradural- Ependymoma or GTR + Recurrence at 9 months 1 year, alive, but
[45] hyperintense/ extramedullary astrocytoma chemotherapy with recurrence 9
enhancement (initially) STR 1 year months after initial
later (due to resection
recurrence)
Lee et al. [39] 39/M 11 months C1-C6 T1W hyperintense/ T2W Intradural- Mutiloculated subdural GTR + adjuvant No evidence of metastatic 17 months, alive
hypointense with extramedullary hematoma (thought to be radiation + disease, no recurrence
homogenous contrast associated with a hidden Interferon
enhancement vascular anomaly or rare
tumor)
Lee et al. [46] 71/F 12 months, C6, C7 T1W hyperintense/T2W Intradural – Neurofibroma or STR No evidence of metastatic NS
worsening over hypointense/mild extramedullary schwannoma disease, no recurrence
(continued on next page)
 Table 1 (continued )

E. Haberfellner et al.
Authors Age Duration of Spinal T1W/T2W Extradural OR Pre-operative diagnosis Treatment Recurrence/metastases Follow-up
(year) (years) symptoms Level (s) /Enhancement on pre- Intradural
and sex operative MRI Extramedullary OR
Intradural
Intramedullary

the prior 2 heterogeneous

months enhancement
Vij et al. [40] 40/M 6 months C1, C2 T1W hyperintense/ T2W Intradural – NS GTR None 1 year, alive
heterointense/ extramedullary
significant enhancement
Kim et al. [18] 34/F NS T4 T1W hyperintense/ T2W Intradural – NS GTR None 3 years, alive
hypointense/ intramedullary
homogenous
enhancement
Jo et al. [7] 68/F 5 days T7,T8 T1W hyperintense/ T2W Extradural Likely metastatic tumor, STR + adjuvant no mets, but invaded the left 6 months, dead
hypointense /significant although no primary was radiation + pedicle, encasing and distorting
enhancement identified Interferon the cord
Fuld et al. 62/M NS (“several C2-C3 T1W hyperintense/ T2W Intradural- Ependymoma STR + adjuvant No mets, no recurrence at 11 11 months, alive
[19] months”) isointense/ intramedullary radiation months
enhancement
Katalinic et al. 30/M NS (“sudden T7-T9 NS Extradural NS GTR + 17 years after surgery, mets to 17 years, dead
[8] bilateral spastic chemotherapy given lungs & bone found (sepsis secondary to
paralysis”) 17 years later when febrile neutropenia
mets were identified on chemo)
Jaiswal et al. 16/M NS C1-C5 T1W hyperintense/ T2W Intradural- NS GTR NS 4 months, alive
[16] hypointense/ with extramedullary
homogenous contrast
enhancement
40/M NS C1-C2 T1W hyperintense/ T2W Intradural- NS GTR NS 4 months, alive
8

hypointense/ intense extramedullary

contrast enhancement
Yu et al. [11] 48/M 6 months C2-C6 T1W hyperintense/ T2W Intradural – Primary cervical STR Brain mets present at the time of 2 months, dead
hypointense/ extramedullary melanoma diagnosis
enhancement
Ganiüsmen 49/F 2 years, L3 NS Intradural – NS GTR + adjuvant Lung nodules found 1 & 5 years 5 years, alive
et al. [61] increasing extramedullary radiation + after surgery
severity over the chemotherapy + INF
prior 6 months therapy
Cicuendez 82/F 1 month L2 T1W hyperintense/ T2W Intradural - NS STR None 2 months, dead
et al. [41] hypointense/ intense extramedullary
homogenous contrast

Clinical Neurology and Neurosurgery 205 (2021) 106649

enhancement
Jeong et al. 42/M 8 months T2–3 T1W hyperintense/ T2W Intradural- NS STR (x2) Lepto-meningeal dissemination 22 months, alive
[47] hypointense/ contrast- extramedullary
enhancement
Sinha et el. 55/M NS L4 NS Extradural Neurofibroma GTR None 38 months, alive
[38]
Cetinalp et al. 47/F NS T9-L1 T1W hyperintense/ T2W Intradural – NS GTR None 19 months alive
[33] isointense intramedullary
Kawanabe 54/F N/A (incidental T12 T1W hyperintense/ T2W Intradural – NS GTR None 60 months, alive
et al. [48] finding) hypointense/ slight extramedullary
enhancement
Li et al. [42] 57/F 1 month T4–5 T1W hyperintense/ T2W Intradural- Complex spinal GTR + adjuvant None 6 months, alive
hyperintense/ moderate extramedullary meningioma chemotherapy
enhancement
Trinh et al. 75/F 3 months T11-L1 Intradural – NS STR + radiation No evidence of metastatic NS
[26] intramedullary disease
(continued on next page)
 Table 1 (continued )

E. Haberfellner et al.
Authors Age Duration of Spinal T1W/T2W Extradural OR Pre-operative diagnosis Treatment Recurrence/metastases Follow-up
(year) (years) symptoms Level (s) /Enhancement on pre- Intradural
and sex operative MRI Extramedullary OR
Intradural
Intramedullary

T1W isointense/
homogenous
enhancement
Mallick et al. 28/M 4 months T8,T9 T1W hyperintense/ T2W Intradural – Meningioma or GTR + radiation + Recurred after 2 years post- 2 years, alive
[17] hypointense/ moderate extramedullary neurogenic tumor chemotherapy surgery at T10; no metastasis (subsequently lost to
contrast enhancement follow-up)
Liu et al. [43] 39/M 2 months C4–5 T1W hyperintense/ T2W Intradural - Schwannoma STR NS 7 months, alive
hypointense/ moderate extramedullary
enhancement
47/M 11 months L2–3 T1W hyperintense/ T2W Intradural – Schwannoma GTR NS 76 months, alive
hypointense/ slight extramedullary
enhancement
76/M 3 weeks T9–10 T1W hyperintense/ T2W Intradural - Schwannoma GTR NS 67 months, alive
hypointense/ moderate extramedullary
contrast enhancement
Wang et al. 60/M 3 months T1, T3–4 T1W hyperintense/ T2W Intradural - NS GTR No recurrence at 19 months 19 months, alive
[49] hypointense/ extramedullary
homogenous contrast
enhancement
Hering et al. 57/F 2 months T12 T1W hyperintense/ T2W Intradural – NS GTR + adjuvant none 24 months, alive
[34] hypointense/ moderate intramedullary radiation
contrast enhancement
Iga et al. [50] 39/M 12 months C1–2+ T1W hyperintense/ T2W Intradural – NS GTR none 24 months, alive
C2–3+ C4–5 hypointense/ strong extramedullary
9

contrast enhancement
Kinnen et al. 54/F NS C2/3 T1W isointense/ T2W Intradural – Pre-op DDx included GTR + adjuvant IFN Dissemination (metastasis) to 54 months, dead
[52] hyperintense/ extramedullary Schwannoma, therapy the brain at 24 months – treated
homogenous Meningioma, or Intradural with whole brain radiation and
enhancement Metastases chemotherapy
64/M 1 year C1/2 T1W isointense/ T2W Intradural - Pre-op DDX included STR 18-month MRI showed stable 18 months, alive
isointense/ extramedullary Meningioma or Metastases tumor extension with decreased
homogeneous ventricle size
enhancement
Sharma et al. 67/F NS L1-L2 T1W hyperintense/ T2W Intradural – NS STR + radiation after recurrence at 9 months 9 months, alive
[51] hypointense extramedullary recurrence at 9
months post-op

Clinical Neurology and Neurosurgery 205 (2021) 106649

Hironaka et al. 39/M 13 months L1-S5 T1W isointense/ T2W Intradural - NS No tx of the primary NS Died 14 months
[3] hyperintense/ extramedullary tumor. after initial
enhancement presentation
Current Study, 62/M 6 months T10–11 T1W hyperintense/ T2W Intradural – intra- and Schwannoma GTR + 5 fractions pf None 15 months, alive
(2020) isointense/ extra-medullary radiotherapy
enhancement
29/M 2 months S1–2 T1W hyperintense/ T2W Intradural - Schwannoma or GTR + Radiotherapy None 24 months, alive
hyperintense/ extramedullary ependymoma
enhancement

C: Cervical, DDx: Differential Diagnosis, F: Female, GTR: Gross total resection, Gy: Gray, L: Lumbar, M: Male, Mets: Metastasis, MRI: Magnetic Resonance Imaging, NOS: Not otherwise specified, NS: Not stated, R: Radiation
adsorbed dose, S: Sacral, STR: Subtotal resection, T: Thoracic, T1W: T1 weighted images, T2W: T2 weighted images, Tx: Treatment.
E. Haberfellner et al.
have different pathologic genetic changes [61]. Primary melanocytic
lesions of the CNS have been shown to commonly carry mutations in
either GNAII Q209L or GNAQ Q209L, which are not seen in melanocytic
lesions that have metastasized to the brain or spinal cord from another
primary site [61]. Conversely, cutaneous melanoma commonly carries
mutations in BRAF V600 or NRAS Q6IK, which have not been demon­
strated in leptomeningeal primaries, limiting the usefulness of available
targeted molecular therapies such as BRAF-inhibitors in the treatment of
PSM [61]. Of the four cases of PSM for which molecular tumor analysis
was performed, there was one report of a positive GNAQ Q209L muta­
tion [19], and one report of a positive GNAII Q209L mutation [52]. In all
four cases, the tumors had a wildtype BRAF gene [19,25,33,52]. Mo­
lecular analysis was unfortunately not completed on the two cases we
report due to limited resources; however, we recommend that it be
completed whenever possible in patients presenting with melanocytic
CNS lesions. This will allow for further characterization of the unique
molecular changes seen in PSM as compared to metastatic tumors, and
could thus lead to a more efficient diagnosis, and to the development of
increasingly targeted therapy for patients with PSM.
3.3. Treatment
Treatment of PSM is not yet standardized, but most experts recom­
mend surgical resection with post-operative radiation [19]. Of the 66
patients reviewed in our study, the majority (53%) were treated with
laminectomy and resection alone (Table 1) [1,8,11–16,18,20,22,29,32,
35,36,38,39,41,43,44,46–50,52,54,58,62]. Thirty five percent were
treated with resection and adjuvant radiation [7,14,19,21–28,30,31,33,
34,42,51,53], while only 6.1% of patients were treated with resection
and chemotherapy, without any adjuvant radiation [12,37,40,45]. One
patient did not receive any treatment [3], and the remaining three
(4.5%) patients were treated with resection and both adjuvant radiation
and chemotherapy [17,31,59]. There were heterogeneous reported
chemotherapeutic agents used in these cases. In three cases, the specific
agent used was not reported [37,40,45]. In one case BCNU, Dacarbazine,
Levamisol and Prednisone were used [12]. In another case, Procarbazin,
CCNU, and Vincristin were used [31], and finally, in a third case,
Tenozolomide was used [59]. Additionally, 6 (9.1%) of the patients
reviewed were treated with adjuvant IFN-therapy (immunotherapy),
alongside resection, with or without adjuvant radiation [7,24,27,34,52,
59]. Due to the paucity of studies reporting the use of immunotherapy in
PSM we could not draw any conclusion regarding its benefit in such
pathology.
Regarding the surgical management of PSM, complete tumor resec­
tion is ideal, as it has been posited to be curative in some cases [14]. Of
the 57 patients that had clearly described surgical resections, 29 (50.9%)
had GTRs [8,14–18,20,29,30,32–35,37,38,40,42–45,48–50,52,59],
compared to 28 (49.1%) who underwent STRs [1,7,11,14,19,22,24,25,
27,28,31,36,38,41,46,47,51–54,62]. Of the 29 patients who had their
tumors resected completely, 26 (89.7%) were alive after a mean
follow-up of 25.5 ± 21.5 months (range, 3–76 months). However, pa­
tients with PSM who under complete resections have been shown to
experience disease recurrence and/or metastasis, with some eventually
dying of the disease [8,17,20,52,59]. In contrast, of the 28 patients that
underwent STR, only 13 (52%) were alive after a mean follow-up of
32 ± 35 months (range, 6–108 months), while 12 were deceased after an
average of 30 ± 45 months (range, 1–136 months). Three patients that
underwent STRs were lost to follow-up [22,25,46]. Of note, even if not
curative or life-extending, STR can reliably relieve symptoms and
improve quality of life. Therefore, safe GTR is recommended and if not
feasible, safe near total resection should be pursued.
Recurrence of the tumor and/or the discovery of new metastases
were managed heterogeneously. There were two cases in which new
metastases were discovered on autopsy [62,63]. There were also many
cases in which the patients deteriorated quickly, declined therapy or
were lost to follow-up, and no treatment was carried out [13,17,28,47,
10
Clinical Neurology and Neurosurgery 205 (2021) 106649
54]. One patient received intrathecal methotrexate [31]. Some patients
received repeat resection, without radiation or systemic therapy [31,
45]. One patient with recurrence was treated with resection and adju­
vant radiation [22], while another was treated with radiation alone
[51]. One patient with brain metastases was treated with whole-brain
radiation and CTLA-4 checkpoint-inhibition [52]. One patient was
treated with IFN and Fotemustine [59]. One patient was treated with the
Dartmouth Regimen, including Decarbazine, Cisplatin, Carmustine, and
Tamoxifen [8]. We cannot comment on the effectiveness of various
therapies for the treatment of recurrence and metastasis due to the
limited number of cases, the variety of treatments utilized, and the
variable follow-up time. However, after excluding the patients who lost
follow-up, the patients that were treated for their metastasis or recur­
rence had increased survival compared to non-treated patients
(57.6 ± 37 months versus 0.9 ± 1.2 months) [13,22,28,31,52,54,59].
Therefore, further treatment for recurrence and/or metastasis is rec­
ommended. However, further research is needed.
3.4. Prognosis
The prognosis of patients with primary CNS melanoma has been
shown to be superior to that of patients with metastatic lesions [40].
While the average survival of patients with cutaneous melanoma that
has metastasized to the CNS is less than 1 year in most studies, Larson
et al., estimated an average post-treatment (surgery and radiation)
life-span of approximately seven years in those with primary CNS lesions
[22]. Survival estimates have however been variable overall, with esti­
mates ranging from a few months to 20 years [64]. Furthermore, these
estimates are limited by the short follow-up periods reported in many
studies [16,44,53]. The difference in prognosis and the favorable
response of PSM to surgical resection makes differentiating primary CNS
lesions from metastases of paramount importance.
3.5. Proposed management algorithm
Based on our extensive literature review and subsequent analysis, we
have created an algorithm to aid clinicians in the diagnosis and man­
agement of PSM (Fig. 5). Clear guidelines for the diagnosis and treat­
ment of this rare tumor, occurring most often in patients presenting with
myelopathic symptoms and characteristic findings on imaging, are key
to ensuring clinicians around the world recognize and manage this
condition appropriately. However, it is important to note that the
definitive diagnosis of PSM requires pathological analysis, as described
previously.
4. Conclusion
In conclusion, we report an exceedingly rare two cases of primary
malignant melanoma of the spine. These tumors present with charac­
teristic imaging findings, but surgical pathology is the only way to
obtain a definitive diagnosis. Early surgical intervention (both for
symptom relief and to obtain a tissue diagnosis) is key to the manage­
ment of these rare and aggressive tumors. GTR should be attempted if
possible, and post-operative radiation can be implemented as needed.
Funding
N/A.
Disclosures
All authors certify that they have no affiliations with or involvement
in any organization or entity with any financial interest (such as hono­
raria; educational grants; participation in speakers’ bureaus; member­
ship, employment, consultancies, stock ownership, or other equity
interest; and expert testimony or patent-licensing arrangements), or
E. Haberfellner et al. Clinical Neurology and Neurosurgery 205 (2021) 106649

Fig. 5. Algorithm for the diagnosis and management of Primary Spinal Melanoma (PSM).

non-financial interest (such as personal or professional relationships, Acknowledgment

affiliations, knowledge or beliefs) in the subject matter or materials
discussed in this manuscript. N/A.

Presentation References

This Manuscript’s abstract was presented at the American Associa­
tion of Neurosurgery (AANS), April 2020, Boston, MA, United States of
America.
[1] D. Farrokh, P. Fransen, D. Faverly, MR findings of a primary intramedullary
malignant melanoma: case report and literature review, AJNR Am. J. Neuroradiol.
22 (2001) 1864–1866.
[2] K. Kakutani, M. Doita, K. Nishida, H. Miyamoto, M. Kurosaka, Radiculopathy due
to malignant melanoma in the sacrum with unknown primary site, Eur. Spine J. .

11
E. Haberfellner et al.
Publ. Eur. Spine Soc. Eur. Spinal Deform. Soc. Eur. Sect. Cerv. Spine Res. Soc. 17
(Suppl 2) (2008) S271–S274, https://doi.org/10.1007/s00586-007-0561-1.
[3] K. Hironaka, K. Tateyama, A. Tsukiyama, K. Adachi, A. Morita, Hydrocephalus
secondary to intradural extramedullary malignant melanoma of spinal cord, World
Neurosurg. 130 (2019) 222–226, https://doi.org/10.1016/j.wneu.2019.07.046.
[4] J.J. Gagnier, G. Kienle, D.G. Altman, D. Moher, H. Sox, D. Riley, CARE Group*, The
CARE guidelines: consensus-based clinical case reporting guideline development,
Glob. Adv. Health Med. 2 (2013) 38–43, https://doi.org/10.7453/
gahmj.2013.008.
[5] A. Liberati, D.G. Altman, J. Tetzlaff, C. Mulrow, P.C. Gøtzsche, J.P.A. Ioannidis,
M. Clarke, P.J. Devereaux, J. Kleijnen, D. Moher, The PRISMA statement for
reporting systematic reviews and meta-analyses of studies that evaluate health care
interventions: explanation and elaboration, PLOS Med. 6 (2009), 1000100, https://
doi.org/10.1371/journal.pmed.1000100.
[6] E. Pappenheim, S.K. Bhattacharji, Primary melanoma of the central nervous
system. Clinical-pathological report of a case, with survey and discussion of the
literature, Arch. Neurol. 7 (1962) 101–113, https://doi.org/10.1001/
archneur.1962.04210020023003.
[7] K.-W. Jo, S.-R. Kim, S.-D. Kim, I.-S. Park, Primary thoracic epidural melanoma: a
case report, Asian Spine J. 4 (2010) 48–51, https://doi.org/10.4184/
asj.2010.4.1.48.
[8] D. Katalinic, B. Anic, R. Stern-Padovan, M. Mayer, M. Sentic, N. Cikes, K. Zarkovic,
S. Dotlic, S. Plestina, Low back pain as the presenting sign in a patient with primary
extradural melanoma of the thoracic spine–a metastatic disease 17 years after
complete surgical resection, World J. Surg. Oncol. 9 (2011) 150, https://doi.org/
10.1186/1477-7819-9-150.
[9] M. Tosaka, M. Tamura, N. Oriuchi, M. Horikoshi, T. Joshita, K. Sugawara,
S. Kobayashi, H. Kohga, T. Yoshida, T. Sasaki, Cerebrospinal fluid
immunocytochemical analysis and neuroimaging in the diagnosis of primary
leptomeningeal melanoma. Case report, J. Neurosurg. 94 (2001) 528–532, https://
doi.org/10.3171/jns.2001.94.3.0528.
[10] T. Wadasadawala, S. Trivedi, T. Gupta, S. Epari, R. Jalali, The diagnostic dilemma
of primary central nervous system melanoma, J. Clin. Neurosci. Off. J. Neurosurg.
Soc. Austral 17 (2010) 1014–1017, https://doi.org/10.1016/j.jocn.2009.12.020.
[11] J. Yu, D.-D. Zhao, S. Chen, J.-M. Zhang, J. Xu, Primary melanoma of the cervical
spine with cerebral metastases: case report and review of the literature, J. Int. Med.
Res. 40 (2012) 1207–1215, https://doi.org/10.1177/147323001204000341.
[12] B. Ozden, O. Barlas, U. Hacihanefioğlu, Primary dural melanomas: report of two
cases and review of the literature, Neurosurgery 15 (1984) 104–107, https://doi.
org/10.1227/00006123-198407000-00020.
[13] W.J. Holaday, E.B. Evans, Spinal (meningeal) melanoma. A case report, J. Bone Jt.
Surg. Am. 50 (1968) 738–742, https://doi.org/10.2106/00004623-196850040-
00009.
[14] D.J. Brat, C. Giannini, B.W. Scheithauer, P.C. Burger, Primary melanocytic
neoplasms of the central nervous systems, Am. J. Surg. Pathol. 23 (1999) 745–754,
https://doi.org/10.1097/00000478-199907000-00001.
[15] A. Sanz-Trelles, I.M. Arranz-Salas, M.I. Valenzuela-Serrano, Melanoma arising in
and limited to a spinal nerve root of the cauda equina, Histopathology 43 (2003)
603–604, https://doi.org/10.1111/j.1365-2559.2003.01679.x.
[16] S. Jaiswal, M. Vij, A. Tungria, A.K. Jaiswal, A.K. Srivastava, S. Behari, Primary
melanocytic tumors of the central nervous system: a neuroradiological and
clinicopathological study of five cases and brief review of literature, Neurol. India
59 (2011) 413–419, https://doi.org/10.4103/0028-3886.82758.
[17] S. Mallick, S. Roy, N.P. Joshi, P.K. Julka, Primary spinal melanoma treated with
adjuvant radiotherapy and concurrent temozolomide: A case report and review of
literature, J. Cancer Res. Ther. 11 (2015) 1027, https://doi.org/10.4103/0973-
1482.151416.
[18] M.S. Kim, D.H. Yoon, D.A. Shin, Primary spinal cord melanoma, J. Korean
Neurosurg. Soc. 48 (2010) 157–161, https://doi.org/10.3340/jkns.2010.48.2.157.
[19] A.D. Fuld, M.E. Speck, B.T. Harris, N.E. Simmons, C.L. Corless, G.J. Tsongalis, D.
A. Pastel, A.C. Hartford, M.S. Ernstoff, Primary melanoma of the spinal cord: a case
report, molecular footprint, and review of the literature, J. Clin. Oncol. Off. J. Am.
Soc. Clin. Oncol. 29 (2011) e499–e502, https://doi.org/10.1200/
JCO.2010.34.0695.
[20] E. Castaner, C. OLIVERAS de la RIVA, L. Barraquer-Bordas, Primitive melanoma of
the cauda equina, Monatsschrift, Psychiatr. Neurol. 120 (1950) 227–236, https://
doi.org/10.1159/000140135.
[21] W. Forbes, A.F.J. Maloney, Primary melanomatosis of the leptomeninx, J. Pathol.
Bacteriol. 62 (1950) 403–409, https://doi.org/10.1002/path.1700620312.
[22] T.C. Larson, O.W. Houser, B.M. Onofrio, D.G. Piepgras, Primary spinal melanoma,
J. Neurosurg. 66 (1987) 47–49, https://doi.org/10.3171/jns.1987.66.1.0047.
[23] K. Salame, O. Merimsky, J. Yosipov, I. Reider-Groswasser, S. Chaitchik, G.
E. Ouaknine, Primary intramedullary spinal melanoma: diagnostic and treatment
problems, J. Neurooncol. 36 (1998) 79–83, https://doi.org/10.1023/a:
1005770929074.
[24] A. Naing, J.L. Messina, F.R. Vrionis, A.I. Daud, Uncommon manifestations of
common malignancies: case 3. Malignant melanoma arising from a spinal nerve
root, J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 22 (2004) 3194–3195, https://doi.
org/10.1200/JCO.2004.09.021.
[25] V. Trinh, R. Medina-Flores, C.L. Taylor, H. Yonas, M.O. Chohan, Primary
melanocytic tumors of the central nervous system: report of two cases and review
of literature, Surg. Neurol. Int. 5 (2014) 147, https://doi.org/10.4103/2152-
7806.142795.
[26] A. Hirano, C.A. Carton, Primary malignant melanoma of the spinal cord,
J. Neurosurg. 17 (1960) 935–944, https://doi.org/10.3171/jns.1960.17.6.0935.
12
Clinical Neurology and Neurosurgery 205 (2021) 106649
[27] T. Yamasaki, H. Kikuchi, J. Yamashita, R. Asato, M. Fujita, Primary spinal
intramedullary malignant melanoma: case report, Neurosurgery 25 (1989)
117–121, https://doi.org/10.1097/00006123-198907000-00023.
[28] F.M. Salpietro, C. Alafaci, O. Gervasio, G. La Rosa, A. Baio, D.C. Francolini,
D. Batolo, F. Tomasello, Primary cervical melanoma with brain metastases. Case
report and review of the literature, J. Neurosurg. 89 (1998) 659–666, https://doi.
org/10.3171/jns.1998.89.4.0659.
[29] P. François, E. Lioret, M. Jan, Primary spinal melanoma: case report, Br. J.
Neurosurg. 12 (1998) 179–182, https://doi.org/10.1080/02688699845384.
[30] J. Bidziński, H. Kroh, C. Leszczyk, P. Bojarski, Primary intraspinal cervical
melanoma, Acta Neurochir. (Wien. ) 142 (2000) 1069–1070, https://doi.org/
10.1007/s007010070066.
[31] D. Freudenstein, A. Wagner, A. Bornemann, U. Ernemann, T. Bauer, F. Duffner,
Primary melanocytic lesions of the CNS: report of five cases, Zent. Neurochir. 65
(2004) 146–153, https://doi.org/10.1055/s-2004-816266.
[32] N.E. Cetinalp, A.E. Yildirim, D. Divanlioglu, D. Belen, An uncommon
intramedullary tumor: primary spinal cord melanoma, Asian Spine J. 8 (2014)
512–515, https://doi.org/10.4184/asj.2014.8.4.512.
[33] K. Hering, A. Bresch, D. Lobsien, W. Mueller, R.-D. Kortmann, C. Seidel, Primary
intradural extramedullary spinal melanoma in the lower thoracic spine, Case Rep.
Oncol. Med. 2016 (2016), 3815280, https://doi.org/10.1155/2016/3815280.
[34] C.-H. Lee, K.Y. Moon, C.K. Chung, H.-J. Kim, K.-H. Chang, S.-H. Park, T.-A. Jahng,
Primary intradural extramedullary melanoma of the cervical spinal cord: case
report, Spine 35 (2010) E303–E307, https://doi.org/10.1097/
BRS.0b013e3181ccb1b3.
[35] M. Vij, S. Jaiswal, A.K. Jaiswal, S. Behari, Primary spinal melanoma of the cervical
leptomeninges: report of a case with brief review of literature, Neurol. India 58
(2010) 781–783, https://doi.org/10.4103/0028-3886.72209.
[36] M. Cicuendez, I. Paredes, P.M. Munarriz, A. Hilario, A. Cabello, A. Lagares, Primary
melanoma of the cauda equina: case report and review of the literature, Neurocir.
Astur. Spain 23 (2012) 112–115, https://doi.org/10.1016/j.neucir.2012.02.003.
[37] Y.-P. Li, H.-Z. Zhang, L. She, X.-D. Wang, L. Dong, E. Xu, X.-D. Wang, Primary
extramedullary spinal melanoma mimicking spinal meningioma: a case report and
literature review, Oncol. Lett. 8 (2014) 339–344, https://doi.org/10.3892/
ol.2014.2099.
[38] Q.-Y. Liu, A.-M. Liu, H.-G. Li, Y.-B. Guan, Primary spinal melanoma of
extramedullary origin: a report of three cases and systematic review of the
literature, Spinal Cord. Ser. Cases 1 (2015) 15003, https://doi.org/10.1038/
scsandc.2015.3.
[39] J.B. Gibson, D. Burrows, W.P. Weir, Primary melanoma of the meninges, J. Pathol.
Bacteriol. 74 (1957) 419–438, https://doi.org/10.1002/path.1700740220.
[40] B. Unal, M. Castillo, MRI features of a primary thoracic epidural melanoma: a case
report, Clin. Imaging 31 (2007) 273–275, https://doi.org/10.1016/j.
clinimag.2007.02.023.
[41] A.B. King, J.W. Chambers, J. Garey, Primary malignant melanoma of the spinal
cord, AMA Arch. Neurol. Psychiatr. 68 (1952) 266–275, https://doi.org/10.1001/
archneurpsyc.1952.02320200104012.
[42] S.-C. Kwon, S.-C. Rhim, D.-H. Lee, S.-W. Roh, S.-K. Kang, Primary malignant
melanoma of the cervical spinal nerve root, Yonsei Med. J. 45 (2004) 345–348,
https://doi.org/10.3349/ymj.2004.45.2.345.
[43] R. Sinha, T.H. Rizvi, S. Chakraborti, C.K. Ballal, A. Kumar, Primary melanoma of
the spinal cord: a case report, J. Clin. Diagn. Res. JCDR 7 (2013) 1148–1149,
https://doi.org/10.7860/JCDR/2013/4893.3037.
[44] G.K. Kounin, K.V. Romansky, L.D. Traykov, P.M. Shotekov, D.Z. Stoilova, Primary
spinal melanoma with bilateral papilledema, Clin. Neurol. Neurosurg. 107 (2005)
525–527, https://doi.org/10.1016/j.clineuro.2004.10.013.
[45] M. Kolasa, D. Jesionek-Kupnicka, R. Kordek, P. Kolasa, Primary spinal cord
melanoma − a case report, Folia Neuropathol. 48 (2010) 212–216.
[46] N.K. Lee, B.H. Lee, Y.J. Hwang, M.-J. Sohn, S. Chang, Y.H. Kim, S.J. Cha, H.J. Cho,
Findings from CT, MRI, and PET/CT of a primary malignant melanoma arising in a
spinal nerve root, Eur. Spine J. Off. Publ. Eur. Spine Soc. Eur. Spinal Deform. Soc.
Eur. Sect. Cerv. Spine Res. Soc. 19 (Suppl 2) (2010) S174–S178, https://doi.org/
10.1007/s00586-010-1285-1.
[47] D.H. Jeong, C.K. Lee, N.K. You, S.H. Kim, K.H. Cho, Primary spinal cord melanoma
in thoracic spine with leptomeningeal dissemination and presenting
hydrocephalus, Brain Tumor Res. Treat. 1 (2013) 116–120, https://doi.org/
10.14791/btrt.2013.1.2.116.
[48] Y. Kawanabe, S. Ueda, N. Sasaki, M. Hoshimaru, Incidental detection of primary
spinal malignant melanoma before central nervous system dissemination, NMC
Case Rep. J. 1 (2014) 24–27, https://doi.org/10.2176/nmccrj.2013-0337.
[49] Y.-B. Wang, W.-J. Wang, H.-T. Zhao, W. Li, T. Peng, X.-F. Zhang, Multiple
melanocytoma of the thoracic spine: a case report and literature review, Spine J.
Off. J. North Am. Spine Soc. 16 (2016) e59–e63, https://doi.org/10.1016/j.
spinee.2015.09.036.
[50] T. Iga, A. Iwanami, T. Funakoshi, S. Mikami, O. Tsuji, N. Nagoshi, E. Okada,
N. Fujita, M. Yagi, K. Watanabe, M. Nakamura, M. Matsumoto, Multifocal primary
melanoma of the cervical spinal cord successfully treated by tumorectomy: a case
report, Spinal Cord. Ser. Cases 4 (2018) 24, https://doi.org/10.1038/s41394-018-
0063-x.
[51] A. Sharma, V.D. Sinha, Primary spinal cord melanoma of intradural extramedullary
origin, J. Neurosci. Rural Pr. 10 (2019) 522–525, https://doi.org/10.1055/s-0039-
1697559.
[52] F. Kinnen, S.K. Fleck, J. Baldauf, V. Hans, G. Daeschlein, E. Rathmann, H.W.
S. Schroeder, S. Marx, Primary leptomeningeal melanocytic tumors of the spine:
report of two cases and review of the literature, World Neurosurg. (2019), https://
doi.org/10.1016/j.wneu.2019.01.015.
E. Haberfellner et al.
[53] A.N. Kanatas, M.D. Bullock, D. Pal, A. Chakrabarty, P. Chumas, Intradural
extramedullary primary malignant melanoma radiographically mimicking a
neurofibroma, Br. J. Neurosurg. 21 (2007) 39–40, https://doi.org/10.1080/
02688690701242235.
[54] F. Schneider, M. Putzier, Primary Leptomeningeal Melanoma, (n.d.) 3.
[55] A.B. Smith, E.J. Rushing, J.G. Smirniotopoulos, Pigmented lesions of the central
nervous system: radiologic-pathologic correlation, Radiogr. Rev. Publ. Radiol. Soc.
N. Am. Inc. 29 (2009) 1503–1524, https://doi.org/10.1148/rg.295095109.
[56] I. Isiklar, N.E. Leeds, G.N. Fuller, A.J. Kumar, Intracranial metastatic melanoma:
correlation between MR imaging characteristics and melanin content, AJR Am. J.
Roentgenol. 165 (1995) 1503–1512, https://doi.org/10.2214/ajr.165.6.7484597.
[57] R.D. Hayward, Malignant melanoma and the central nervous system. A guide for
classification based on the clinical findings, J. Neurol. Neurosurg. Psychiatr. 39
(1976) 526–530, https://doi.org/10.1136/jnnp.39.6.526.
[58] W.W. Dzwierzynski, Managing malignant melanoma, Plast. Reconstr. Surg. 132
(2013) 446e–460ee, https://doi.org/10.1097/PRS.0b013e31829ad411.
[59] O. Ganiüsmen, F.D. Özer, M. Mete, N. Özdemir, Ü. Bayol, Slow progression and
benign course of a primary malign melanoma of a lumbar nerve root, Clin. Neurol.
Neurosurg. 114 (2012) 166–168, https://doi.org/10.1016/j.clineuro.2011.09.012.
13
Clinical Neurology and Neurosurgery 205 (2021) 106649
[60] L. Cheng, A. Lopez-Beltran, F. Massari, G.T. MacLennan, R. Montironi, Molecular
testing for BRAF mutations to inform melanoma treatment decisions: a move
toward precision medicine, Mod. Pathol. Off. J. U. S. Can. Acad. Pathol. Inc. 31
(2018) 24–38, https://doi.org/10.1038/modpathol.2017.104.
[61] J. van de Nes, M. Gessi, A. Sucker, I. Möller, M. Stiller, S. Horn, S.L. Scholz,
C. Pischler, N. Stadtler, B. Schilling, L. Zimmer, U. Hillen, R.A. Scolyer, M.
E. Buckland, L. Lauriola, T. Pietsch, A. Waha, D. Schadendorf, R. Murali, K.
G. Griewank, Targeted next generation sequencing reveals unique mutation profile
of primary melanocytic tumors of the central nervous system, J. Neurooncol. 127
(2016) 435–444, https://doi.org/10.1007/s11060-015-2052-2.
[62] F.W. Kiel, L.B. Starr, J.L. Hansen, Primary melanoma of the spinal cord,
J. Neurosurg. 18 (1961) 616–629, https://doi.org/10.3171/jns.1961.18.5.0616.
[63] J.H. Clifford, H.G. McClintock, A.E. Lubchenco, Primary spinal cord malignant
melanoma: case report, J. Neurosurg. 29 (1968) 410–413, https://doi.org/
10.3171/jns.1968.29.4.0410.
[64] M. Nishihara, T. Sasayama, T. Kondoh, K. Tanaka, E. Kohmura, H. Kudo, Long-term
survival after surgical resection of primary spinal malignant melanoma, Neurol.
Med. Chir. (Tokyo). 49 (2009) 546–548, https://doi.org/10.2176/nmc.49.546.

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DOI: 10.12998/wjcc.v9.i10.2352
Primary intramedullary melanoma of lumbar spinal cord: A case
report
Le-Dong Sun, Xin Chu, Li Xu, Xiu-Zhen Fan, Yi Qian, Da-Ming Zuo
ORCID number: Le-Dong Sun 0000-
0003-4129-4204; Xin Chu 0000-0002-
7853-1296; Li Xu 0000-0003-2071-
6922; Xiu-Zhen Fan 0000-0001-8696-
8132; Yi Qian 0000-0003-3779-6973;
Da-Ming Zuo 0000-0003-2003-9474.
Author contributions: Sun LD and
Qian Y designed the study; Chu X
helped prepare the radiology
images; Xu L and Fan XZ analyzed
the pathology images; Zuo DM
wrote the manuscript; all authors
read and approved the final
manuscript.
Supported by Foundation of the
President of the Fifth Affiliated
Hospital, Southern Medical
University, 2020.
Informed consent statement:
Written informed consent was
obtained from the patient for
publication of this case report and
accompanying images.
Conflict-of-interest statement: The
authors have no conflicts of
interest to report.
CARE Checklist (2016) statement:
We have read the CARE Checklist
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prepared and revised according to
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WJCC https://www.wjgnet.com
World Journal of
Clinical Cases
World J Clin Cases 2021 April 6; 9(10): 2352-2356
ISSN 2307-8960 (online)
CASE REPORT
Le-Dong Sun, Xin Chu, Li Xu, Xiu-Zhen Fan, Department of Dermatology, The Fifth Affiliated
Hospital, Southern Medical University, Guangzhou 510900, Guangdong Province, China
Yi Qian, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou 510900,
Guangdong Province, China
Da-Ming Zuo, Department of Medical Laboratory, Southern Medical University, Guangzhou
510515, Guangdong Province, China
Corresponding author: Yi Qian, MD, Associate Professor, The Fifth Affiliated Hospital,
Southern Medical University, No. 566 Congcheng Avenue, Conghua District, Guangzhou
510900, Guangdong Province, China. 1328059119@qq.com
Abstract
BACKGROUND
Primary intramedullary melanoma is a very rare tumor, most frequently
occurring in the cervical and thoracic spinal cord.
CASE SUMMARY
We present a rare case in which the primary intramedullary melanoma was
located in the lumbar spine. A 56-year-old man complained of progressive
intermittent pain in the lumbar area. Thoracic magnetic resonance imaging
showed a spinal intramedullary tumor between the L3 and S1 levels. The tumor
was resected entirely, and the diagnosis of malignant melanoma was confirmed
by histopathology.
CONCLUSION
Primary melanoma of the spinal cord, particularly intramedullary localization,
has rarely been reported in the previous literature. We describe a primary
malignant melanoma of the lumbar spinal cord and discuss the challenges
associated with the diagnosis.
Key Words: Intramedullary melanoma; Spinal cord; Lumbar; Magnetic resonance imaging;
Histopathological examination; Immunohistochemical staining; Case report
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2352 April 6, 2021 Volume 9 Issue 10

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WJCC https://www.wjgnet.com
Sun LD et al. Primary intramedullary melanoma
Core Tip: We report a primary malignant melanoma of the lumbar spinal cord and
emphasize the diagnostic challenge.
Citation: Sun LD, Chu X, Xu L, Fan XZ, Qian Y, Zuo DM. Primary intramedullary melanoma
of lumbar spinal cord: A case report. World J Clin Cases 2021; 9(10): 2352-2356
URL: https://www.wjgnet.com/2307-8960/full/v9/i10/2352.htm
DOI: https://dx.doi.org/10.12998/wjcc.v9.i10.2352
INTRODUCTION
Primary malignant melanoma of the central nervous system (CNS) accounts for about
1% of all melanoma cases[1]. Primary CNS melanoma localized to the spinal cord is
extremely rare, and most frequently involves the thoracic spine and the cervical spine.
The diagnosis of primary intramedullary melanoma was based on histological
examination and the exclusion of other lesions outside of the CNS[2,3]. In this paper, we
present the case of a 56-year-old male patient diagnosed with primary intramedullary
melanoma of the lumbar spine that proceeded with surgical resection.
CASE PRESENTATION
Chief complaints
A 56-year-old man visited our hospital with radiating pain in the lower limbs for 2 wk.
History of past illness
The patient had been suffering from progressive intermittent pain in the lumbar area
for approximately 3 years, and his pain was only partially relieved after bed rest. He
then began to feel severe radiating pain in the left lower limb 2 wk before presentation.
Physical examination
The patient had mild kyphosis of the spine and intervertebral tenderness in the L4-L5
and L5-S1 disc spaces. Physical examination showed left hip tenderness and
percussion pain. The muscles of the left lower limb were significantly atrophied
relative to the right lower limb. Resultantly, the left lower limb was observed to be 3
cm shorter than the right one.
A Faber test of the left lower limb was positive. Straight leg elevation tests of both
lower extremities were negative. Pain sensation and temperature sensation were
normal in both lower limbs. Muscle tension in both lower extremities was also normal.
Dorsiflexion force of the left ankle joint was 3+, and plantar flexor muscle strength
was level 3. The nail of the big toe was grade 0. Right ankle dorsiflexor force was 4,
and plantar flexor force was 5. The anal sphincter contracted evenly and forcefully.
Bilateral knee and Achilles tendon reflexes were normal. The physiological reflex was
present, but the pathological reflex was not elicited.
Imaging examinations
Magnetic resonance imaging (MRI) analysis of the lumbar spine exhibited an
intramedullary mass between the L3 and S1 levels. An impressive Schmorl node was
visible in the L4 vertebral body (Figure 1).
Histopathological examination
Histopathological examination of the specimen showed that the tissue was composed
of most polygonal and some spindle tumor cells. The tumor cells were relatively
uniform in size, with rich and transparent cytoplasm. The nuclei of most of the cells
were either round or oval, and they had large nucleoli. The tumor cells displayed a
high degree of mitotic activity, but no necrosis was seen (Figure 2A). The isolated
tumor was also subjected to immunohistochemical examination, which revealed
positive staining for S-100, homatropine methylbromide (HMB)-45, and p53,
indicating an intramedullary malignant melanoma (Figure 2B-D). The tumor cells
expressed vimentin and did not exhibit positivity for the epithelial marker cytokeratin,
2353 April 6, 2021 Volume 9 Issue 10
Sun LD et al. Primary intramedullary melanoma

Figure 1 Magnetic resonance imaging analysis of spinal cord lesion. A: Sagittal T1-weighted magnetic resonance imaging (MRI); B: Sagittal T2-
weighted MRI; C: Homogeneous contrast enhancement on axial T1-weighted images with gadolinium.

which indicates that the tumor had undergone the epithelial-to-mesenchymal

transition process (Figure 2E and F). Additionally, immunostaining for Ki67 supported
an appreciable proliferative activity, and the Ki67 proliferation index was about 10%-
50% (Figure 2G).

FINAL DIAGNOSIS
The patient had no history or clinical manifestation of the primary cutaneous or ocular
lesion. Based on the MRI analysis and histological examination, the final diagnosis was
primary malignant intramedullary melanoma of the lumbar spinal cord.

TREATMENT
The patient underwent L4-S1 discectomy with total resection of a dark reddish-brown
ventrally exophytic intramedullary tumor. The tumor was exposed after the dura was
widely opened. It was black and firm, and invaded the L5 spinal nerve root. Titanium
mesh implantation and pedicle screw fixation were used for the treatment.

OUTCOME AND FOLLOW-UP

The patient refused the molecular targeted therapy based on the drug sensitivity test.
Unfortunately, the patient passed away 6 mo after the surgery.

WJCC https://www.wjgnet.com 2354 April 6, 2021 Volume 9 Issue 10

 Sun LD et al. Primary intramedullary melanoma

Figure 2 Histological analysis of the tumor tissue. A: Hematoxylin and eosin staining showing the tumor cells (× 200); B-G: Immunohistochemical staining for
S-100, homatropine methylbromide-45, p53, vimentin, cytokeratin, and Ki67, respectively (× 400).

DISCUSSION
Our case presents a rare occurrence of primary intramedullary malignant melanoma in
the lumbar spine manifested by pathological features and clinical behavior. Primary
malignant melanoma of the spinal cord is common in the thoracic region and the
cervical region.
Melanoma is an aggressive form of cancer that develops in the cells (melanocytes)
that produce melanin and can show up anywhere on the skin[4]. Less common types
may be found in other organs. Primary melanoma in the CNS arises from melanocytes
that develop from their precursors. Hayward's classification of primary spinal cord
melanoma relies on the absence of a melanoma outside of the spinal cord and
histologic confirmation of melanoma[2]. Primary intramedullary melanoma shows
either slow progression or rapid decline, and this lesion is distinct from meningeal
melanocytoma and the frequent type of skin melanoma with metastases extending to
the CNS.
Notably, surgical criteria are useful when distinguishing primary malignant
melanoma from meningeal melanocytoma. At surgery, the adherence to nerve roots by
the tumor is suggestive of primary spinal melanoma[5]. Additional chemotherapy and
adjuvant radiotherapy may improve disease-free survival[3]. Accordingly, it was
believed that our case was associated with a primary spinal cord melanoma.
So far, MRI analysis is the best imaging modality for diagnosing spinal cord tumors.
Spinal cord melanoma often displays slightly greater signal intensity on the T1-
weighted images than the otherwise healthy spinal cord. On the T2-weighted images,
however, it can show the same or less signal intensity than the normal cord. The lesion
usually shows mild and homogeneous enhancement following the intravenous
administration of a gadolinium-based contrast agent. Here, the appearance of the
lesion on MRI in our case was consistent with previously reported findings[6,7]. The
final diagnosis should be based on histological and immunophenotyping

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Sun LD et al. Primary intramedullary melanoma

examinations. Histopathologic features of malignant melanoma include the formation

of tight nests surrounded by well-differentiated melanocytes, which produce
pigmented melanin[8]. Immunohistochemically, S-100 and HMB-45 may contribute to
the diagnosis of malignant melanoma[9].
The various differential diagnoses of primary intramedullary melanoma include
metastatic carcinoma, epithelioid schwannoma, and meningeal melanocytoma. In the
diagnosis of spinal cord melanoma, the distinction between primary intramedullary
melanoma and metastatic melanoma is necessary. As mentioned in the Hayward
criteria[2], histological confirmation and exclusion of melanoma outside the CNS (e.g.,
the skin, squamous mucosa, and the eyes) are required for the diagnosis of primary
intramedullary melanoma. In contrast to melanomas, epithelioid schwannomas exhibit
compactly interwoven fascicles of pigmented spindle cells with oval nuclei and low
nuclear grade[10]. Meningeal melanocytoma is a rare pigmented CNS tumor that might
be intradural or extradural and was frequently found in the posterior cranial fossa and
spinal cord[11]. Histologically, the tumor cells are arranged in sheets, bundles, nests,
and whorls surrounded by a network of reticulin fibers. Mitosis and necrosis are rarely
seen in the meningeal melanocytomas.

CONCLUSION
We herein report a case of primary intramedullary melanoma of the lumbar spinal
cord, which is a very rare disease, and surgical resection was applied to the patient
after careful evaluation.

REFERENCES
1 Liubinas SV, Maartens N, Drummond KJ. Primary melanocytic neoplasms of the central nervous
system. J Clin Neurosci 2010; 17: 1227-1232 [PMID: 20558070 DOI: 10.1016/j.jocn.2010.01.017]
2 Hayward RD. Malignant melanoma and the central nervous system. A guide for classification based
on the clinical findings. J Neurol Neurosurg Psychiatry 1976; 39: 526-530 [PMID: 950562 DOI:
10.1136/jnnp.39.6.526]
3 Sharma A, Sinha VD. Primary Spinal Cord Melanoma of Intradural Extramedullary Origin. J
Neurosci Rural Pract 2019; 10: 522-525 [PMID: 31595127 DOI: 10.1055/s-0039-1697559]
4 Mirea MA, Eckensperger S, Hengstschläger M, Mikula M. Insights into Differentiation of
Melanocytes from Human Stem Cells and Their Relevance for Melanoma Treatment. Cancers (Basel)
2020; 12 [PMID: 32899370 DOI: 10.3390/cancers12092508]
5 Liu QY, Liu AM, Li HG, Guan YB. Primary spinal melanoma of extramedullary origin: a report of
three cases and systematic review of the literature. Spinal Cord Ser Cases 2015; 1: 15003 [PMID:
28053708 DOI: 10.1038/scsandc.2015.3]
6 Yamasaki T, Kikuchi H, Yamashita J, Asato R, Fujita M. Primary spinal intramedullary malignant
melanoma: case report. Neurosurgery 1989; 25: 117-121 [PMID: 2755570 DOI:
10.1097/00006123-198907000-00023]
7 Uematsu Y, Yukawa S, Yokote H, Itakura T, Hayashi S, Komai N. Meningeal melanocytoma:
magnetic resonance imaging characteristics and pathological features. Case report. J Neurosurg 1992;
76: 705-709 [PMID: 1545267 DOI: 10.3171/jns.1992.76.4.0705]
8 Bastian BC. The molecular pathology of melanoma: an integrated taxonomy of melanocytic
neoplasia. Annu Rev Pathol 2014; 9: 239-271 [PMID: 24460190 DOI:
10.1146/annurev-pathol-012513-104658]
9 Xia J, Wang Y, Li F, Wang J, Mu Y, Mei X, Li X, Zhu W, Jin X, Yu K. Expression of
microphthalmia transcription factor, S100 protein, and HMB-45 in malignant melanoma and
pigmented nevi. Biomed Rep 2016; 5: 327-331 [PMID: 27602212 DOI: 10.3892/br.2016.732]
10 Hart J, Gardner JM, Edgar M, Weiss SW. Epithelioid Schwannomas: An Analysis of 58 Cases
Including Atypical Variants. Am J Surg Pathol 2016; 40: 704-713 [PMID: 26752543 DOI:
10.1097/PAS.0000000000000589]
11 Shanthi V, Ramakrishna BA, Bheemaraju VV, Rao NM, Athota VR. Spinal meningeal
melanocytoma: A rare meningeal tumor. Ann Indian Acad Neurol 2010; 13: 308-310 [PMID:
21264144 DOI: 10.4103/0972-2327.74192]

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 Open Access Case
Report
Review began 06/17/2021
Review ended 06/25/2021
Published 07/05/2021
© Copyright 2021
Tuz Zahra et al. This is an open access
article distributed under the terms of the
Creative Commons Attribution License
CC-BY 4.0., which permits unrestricted
use, distribution, and reproduction in any
medium, provided the original author and
source are credited.
How to cite this article
Tuz Zahra F, Ajmal Z, Qian J, et al. (July 05, 2021) Primary Intramedullary Spinal Melanoma: A Rare Disease of the Spinal Cord. Cureus 13(7):
e16194. DOI 10.7759/cureus.16194
DOI: 10.7759/cureus.16194
Primary Intramedullary Spinal Melanoma: A Rare
Disease of the Spinal Cord
Fatima Tuz Zahra 1 , Zainub Ajmal 1 , Jiang Qian 2 , Stephen Wrzesinski 3
1. Internal Medicine, Albany Medical Center, Albany, USA 2. Pathology, Albany Medical Center, Albany, USA 3.
Hematology and Medical Oncology, Albany Medical Center, Albany, USA
Corresponding author: Fatima Tuz Zahra, dr.fatimatuzzahra1611@gmail.com
Abstract
Primary malignant melanoma of the intramedullary region of the spinal cord has rarely been reported in the
literature. These tumors can have variable appearance on magnetic resonance imaging (MRI) due to
different extents of melanin and hemorrhage. Histopathologic confirmation and a comprehensive workup to
rule out extra-spinal melanoma are required to make definitive diagnosis. We present a case of a patient
diagnosed with primary intramedullary spinal melanoma in his lower thoracic spinal cord who was
effectively treated with surgical resection, adjuvant radiation, and adjuvant immunotherapy. Gross total
resection (GTR) is most vital in the management of this spinal tumor. Although several studies have
established the efficacy of immunotherapy agents in advanced malignant melanoma, the use of these agents
has not been studied in primary central nervous system melanomas. This case provides insight into the
diagnostic approach and treatment options for this unique malignancy.
Categories: Neurology, Neurosurgery, Oncology
Keywords: primary spinal melanoma, non cutaneous malignant melanoma, adjuvant radiation therapy, cancer-
immunotherapy, rare brain tumors, neuro oncology
Introduction
Primary melanoma of the central nervous system (CNS) is a rare neoplasm that accounts for approximately
1% of all cases of melanoma [1]. Primary intramedullary spinal cord melanoma is an extremely unique entity
[2]. Diagnosis requires histopathological confirmation and ruling out metastatic spread from skin, ocular, or
gastrointestinal primary lesions [3]. Surgical resection is the mainstay of treatment but due to rarity of the
tumor, there are no well-defined guidelines for using available adjuvant therapies [2]. We present a case of
primary intramedullary spinal melanoma treated with gross total resection and adjuvant radiation therapy
followed by adjuvant immunotherapy with Nivolumab yielding favorable outcome.
Case Presentation
A 61-year-old male with no significant past medical history was seen by Neurology as an outpatient for
evaluation of progressive lower extremity weakness, numbness and paresthesia, present for one year. He
also complained of saddle paresthesia associated with urinary retention and stool incontinence. These
symptoms had progressively worsened over several months with decreased lower extremity strength
resulting in multiple falls.
On physical examination, the patient had asymmetric motor weakness in his bilateral lower extremities,
worse on the right side. Complete loss of right hip abduction and right-sided foot drop was also noted. The
patient had hypesthesia to temperature, proprioception, and vibration below the T11 sensory level. Deep
tendon reflexes were normal.
Magnetic resonance imaging (MRI) studies of the cervical and lumbosacral spine revealed no abnormalities
that could explain patient’s symptoms. MRI of thoracic spine with contrast demonstrated an expansile,
intramedullary lesion in the thoracic cord at the levels T10 and T11. There was minimal hyperintense T1
signal, suggestive of intrinsic hemorrhage (Figure 1), and moderate enhancement with intravenous contrast
(Figure 2). There was a slight increase in signal on T2 weighted sequences (Figure 3). This raised concern for
a spinal cord malignancy like ependymoma, astrocytoma, hemangioblastoma, melanoma, or metastatic
disease.
 FIGURE 1: MRI of thoracic spine, T1 sagittal view.
Minimal hyperintense T1 signal, suggesting intrinsic hemorrhage.

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 2 of 11

 FIGURE 2: MRI of thoracic spine, T1 sagittal view with intravenous
contrast and fat suppression.
Moderate enhancement on intra-medullary lesion with intravenous contrast.

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 3 of 11

 FIGURE 3: MRI of thoracic spine, T2 sagittal view.
A slight hyperintense signal on T2 weighted sequence can be visualized.

Patient underwent a T9-T11 laminectomy and resection of this T10-T11 intramedullary tumor using
ultrasonographic spinal neuro-navigation, neurophysiological monitoring, and intradural operative
microscope. Gross total resection (GTR) was achieved. A dark brown-green colored tumor was visualized and
sent for intra-operative frozen section pathologic analysis which revealed an epithelioid neoplasm with
marked pigment deposition. On histopathology, the tumor was demarcated from spinal cord tissue and was
composed of nests of medium- to large-sized cells with prominent nucleoli, low N-C (nuclear to
cytoplasmic) ratio, appreciable mitotic activity, and fine granular cytoplasmic melanin pigments (Figure 4).
Immunohistochemically, the tumor was positive for S-100 protein, Melan-A or MART-1 (Figure 5) and MITF
(Figure 6), confirming malignant melanoma. There was prominent lymphoplasmacytic reaction to the tumor,
together with hemosiderin deposits indicating prior hemorrhage. Subsequent workup including a careful
skin exam, ophthalmological evaluation, and whole-body PET-CT revealed no evidence of extra-spinal
malignancy. Of note, the patient had a colonoscopy before GTR that had not shown any evidence of
melanoma in colonic mucosa. However, an upper gastrointestinal endoscopy was deferred in this case due to
the high risk of complications after spinal surgery. Given the above workup, the patient was diagnosed with
Primary intramedullary malignant melanoma of thoracic spine.

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 4 of 11

 FIGURE 4: Low and high-power view of H&E stained sections.
Melanoma in cellular nests composed of large cells with prominent nucleoli but low N-C ratio, with pigments
present in some tumor cells. H&E: hematoxylin and eosin.

FIGURE 5: IHC stain for MART-1/Melan-A.

IHC shows cytoplasmic staining in melanoma cells. IHC: immunohistochemistry.

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 5 of 11

 FIGURE 6: IHC stain for MITF.
IHC shows nuclear staining in melanoma cells. MITF: microphthalmia-associated transcription factor; IHC:
immunohistochemistry.

After GTR, the patient received adjuvant radiation therapy to the lower thoracic spine surgical bed and
completed a total dose of 5040cGy in twenty-eight fractions. Adjuvant checkpoint inhibitor therapy with
nivolumab was subsequently administered at 480 mg intravenously every four weeks. The patient tolerated
eleven of thirteen cycles of nivolumab after which it was discontinued when he developed grade III
pneumonitis (immune-related adverse effect) that was effectively treated with high dose steroid therapy that
was tapered over several weeks. Fifteen months after initial spinal surgery patient’s lower extremity
weakness, hypesthesia, and sphincter dysfunction has nearly resolved. Most recent surveillance MRI scan
performed 12 months after spinal surgery showed no evidence of disease recurrence (Figures 7, 8, 9). The
patient continues to follow-up regularly with Oncology.

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 6 of 11

 FIGURE 7: MRI of thoracic spine, T1 sagittal view.
No evidence of disease recurrence.

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 7 of 11

 FIGURE 8: MRI of thoracic spine, T1 sagittal view with intravenous
contrast and fat suppression
No evidence of disease recurrence.

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 8 of 11

 FIGURE 9: MRI of thoracic spine, T2 sagittal view.
No evidence of disease recurrence.

Discussion
Primary CNS melanoma is a malignant tumor that was first described by Hirschberg in 1906 [4]. This rare
entity accounts for only 1% of all melanomas and has an estimated incidence of 0.005 cases per
100,000. Oncogenesis is hypothesized to occur from neural crest cells that fail to migrate during
embryogenesis and reside in the neural tube. Later in life, dysregulated signaling between these neural crest
cells and adjacent cells causes disruption in normal differentiation and maturation of these cells. It has also
been hypothesized that primary CNS melanoma in atypical sites may stem from melanocyte precursors that
accompany the pial sheaths of vascular bundles. Oncogenesis from neuroectodermal cells with
abnormalities in cellular migration has also been suggested [5,6]. Primary spinal melanoma(PSM) is even
more unique and most of its cases seem to arise in the thoracic spinal cord [7]. Location of these tumors can
be intra- or extramedullary, leptomeningeal, or extradural. Intramedullary location of the neoplasm, as seen
in our case, is very rare [1]. Few population studies on primary CNS melanomas published to date show a
similar predisposition of males and females to be affected with peak incidence reported in the fifth decade
of life [2,8]. Symptoms of PSM depend on exact location of the tumor and are usually sub-acute or insidious
in presentation, except in case of hemorrhage which may cause acute worsening of neurological symptoms.
Patients may present with neck or back pain, signs of progressive asymmetric sensory and motor
myelopathy, or sphincter dysfunction [9].

Factors to be considered in diagnosis of primary CNS melanoma were first described by Hayward in 1976:
absence of other CNS tumors, lack of extra-CNS lesions, and pathological confirmation [3]. The diagnostic
approach to primary spinal melanoma is based on excluding primary site of origin outside the spinal cord for
which a thorough ophthalmologic, dermatologic, and gastrointestinal examination is required [10]. In our
patient, a comprehensive eye exam, skin inspection, and colonoscopy did not reveal an extra-spinal primary
leading to the diagnosis of primary spinal melanoma. MRI is the imaging modality of choice for diagnosis but
there are no distinct MRI findings that can differentiate primary spinal melanoma from other pigmented
tumors of the spinal cord such as extra-spinal metastatic melanoma, and hemorrhagic neoplasms, like
ependymoma and astrocytoma. The imaging features of primary spinal melanoma can vary depending on
the extent of melanocytic content and based on the absence or presence of hemorrhage. Most lesions show
hyperintense signals on T1-weighted images while the T2-weighted images may demonstrate iso or
hypointense signals compared to normal cord. Homogeneous pattern of enhancement on gadolinium post-
contrast images has often been reported but sometimes the pattern can be peripheral, inhomogeneous, or
nodular [1,6,11]. Malignant melanomas have high metabolic activity and function and a PET/CT is helpful

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 9 of 11

 for the evaluation of local versus metastatic spread from distant disease [12]. None of these imaging
modalities are highly specific, therefore a definitive diagnosis of PSM is made on pathologic studies.
Hyperplastic sheets of spindled or epithelioid cells can be seen and may show significant pleomorphism.
Most tumors have some degree of cytoplasmic melanin but rare instances of amelanotic melanoma have
been reported. Other features like prominent nucleoli, atypical mitoses, tissue invasion, and necrosis can be
seen as well [6,13]. Key immunohistochemical markers for diagnosis include human melanoma black-
45(HMB-45): a marker of melanocytic differentiation and melanosome formation, S-100 protein, Melan-A:
melanocytic lineage-specific marker, and microphthalmia-associated transcription factor(MITF): a major
transcriptional regulator of the melanocytic cell lineage [13-15].

In our patient, minimal T1 hyperintensity and moderate enhancement after intravenous contrast was
characteristic of malignant melanoma. PET/CT scan demonstrated a primary spinal cord lesion and
pathologic findings consolidated the diagnosis of primary malignant melanoma of the spine.

Because, PSM is a rare tumor, there are no definitive guidelines for its treatment. Overwhelming consensus
based on published literature favors gross total resection (GTR) as cornerstone of treatment. GTR yields
improved survival and mortality outcomes. Adjuvant radiation treatment (RT) with GTR may decrease odds
of local recurrence compared to GTR alone but Zhang et al. did not observe any added survival benefit [2].
Puyana et al. concluded that compared to GTR, sub-total resection (STR) does not offer a survival benefit
without addition of adjuvant radiation therapy (RT) and hence in such cases where a complete surgical
excision or GTR is not possible, adjuvant radiation becomes a more vital element of treatment, akin to the
treatment of resected cutaneous melanomas with positive margins without further surgery being feasible [8].
Surgical excision either GTR or STR improves overall survival compared to biopsy alone. The role of
adjuvant systemic therapy remains less clear. However, adjuvant systemic therapy is generally administered
in combination with surgical excision and adjuvant radiation. Case studies have shown variable survival
outcomes with use of adjuvant dacarbazine or temozolomide [16]. Improved disease control and survival
with the use of high dose systemic interferon (INF)-beta or INF-alpha has also been described in few cases
[17]. Novel biologics and targeted therapies are promising and have a favorable side effect profile than
cytotoxic chemotherapies. Targeted therapy agents like dabrafenib and vemurafenib can be effective
adjuvant agents in patients with BRAF mutant melanomas [18]. Immune checkpoint inhibitor therapy with
cytotoxic T lymphocyte antigen-4 inhibitor Ipilimumab and programmed death-1 inhibitors Nivolumab and
Pembrolizumab has shown positive outcomes in patients with advanced melanomas [19]. Efficacy in primary
spinal melanoma has not been established. Oncogenic mutations in ROS-1, ALK, NRAS, P13K/AKT/mTOR
pathway, and GNAQ and GNA11 genes are also being investigated for therapeutic potential with targeted
agents [20]. In the case of our patient, complete surgical resection, adjuvant radiation therapy and adjuvant
immunotherapy with Nivolumab has shown a promising outcome in the form of recurrence-free survival
over 15 months since surgery, suggesting a triple modality approach may be an effective option for the
management of patients with this rare disease.

Conclusions
Primary intramedullary spinal melanoma is extremely rare and often arises from thoracic spinal cord.
Characteristic MRI findings can indicate spinal melanoma, but a definitive diagnosis of primary spinal
melanoma needs pathologic confirmation and ruling out extra-spinal melanoma. GTR should always be
attempted to yield most promising survival and mortality outcomes. Adjuvant radiation limits local
recurrence but the role of adjuvant chemotherapy, targeted therapy, and immunotherapy to decrease the
risk of developing distant disease needs to be explored further. Our case provides a unique insight into
benefits of adjuvant immunotherapy with Nivolumab in addition to GTR and RT, and highlights a shifting
paradigm in CNS melanoma treatment options.

Additional Information
Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In
compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services
info: All authors have declared that no financial support was received from any organization for the
submitted work. Financial relationships: All authors have declared that they have no financial
relationships at present or within the previous three years with any organizations that might have an
interest in the submitted work. Other relationships: All authors have declared that there are no other
relationships or activities that could appear to have influenced the submitted work.

References
1. Farrokh D, Fransen P, Faverly D: MR findings of a primary intramedullary malignant melanoma: case report
and literature review. Am J Neuroradiol. 2001, 22:1864-6.
2. Zhang M, Liu R, Xiang Y, Mao J, Li G, Ma R, Sun Z: Primary spinal cord melanoma: a case report and a
systemic review of overall survival. World Neurosurg. 2018, 114:408-20. 10.1016/j.wneu.2018.03.169
3. Hayward RD: Malignant melanoma and the central nervous system. A guide for classification based on the
clinical findings. J Neurol Neurosurg Psychiatry. 1976, 39:526-30. 10.1136/jnnp.39.6.526

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 10 of 11

 4. Hirschberg A: Chromatophoroma medullae spinalis, ein Beitrag zur Kenntnis der primären
Chromatophorome des Zentralnervensystems. Virchows Archiv für pathologische Anatomie und Physiologie
und für klinische Medizin. 1906, 186:229-40. 10.1515/9783112385005-010
5. Liubinas SV, Maartens N, Drummond KJ: Primary melanocytic neoplasms of the central nervous system . J
Clin Neurosci. 2010, 17:1227-32. 10.1016/j.jocn.2010.01.017
6. Agarwalla PK, Koch MJ, Mordes DA, Codd PJ, Coumans JV: Pigmented lesions of the nervous system and the
neural crest: lessons from embryology. Neurosurgery. 2016, 78:142-55. 10.1227/NEU.0000000000001010
7. Smith AB, Rushing EJ, Smirniotopoulos JG: Pigmented lesions of the central nervous system: radiologic-
pathologic correlation. Radiographics. 2009, 29:1503-24. 10.1148/rg.295095109
8. Puyana C, Denyer S, Burch T, Bhimani AD, McGuire LS, Patel AS, Mehta AI: Primary malignant melanoma
of the brain: a population-based study. World Neurosurg. 2019, 130:e1091-7. 10.1016/j.wneu.2019.07.095
9. Corrêa DG, dos Santos RQ, Hygino da Cruz LC: Primary intramedullary malignant melanoma: can imaging
lead to the correct diagnosis?. J Int Med Res. 2020, 48:0300060520966152. 10.1177/0300060520966152
10. Wu L, Xu Y: Primary spinal intramedullary malignant melanoma involving the medulla oblongata . Spine J.
2016, 16:e499-500. 10.1016/j.spinee.2016.01.079
11. Salpietro FM, Alafaci C, Gervasio O, et al.: Primary cervical melanoma with brain metastases. Case report
and review of the literature. J Neurosurg. 1998, 89:659-66. 10.3171/jns.1998.89.4.0659
12. Branstetter BF 4th, Blodgett TM, Zimmer LA, Snyderman CH, Johnson JT, Raman S, Meltzer CC: Head and
neck malignancy: is PET/CT more accurate than PET or CT alone?. Radiology. 2005, 235:580-6.
10.1148/radiol.2352040134
13. Koelsche C, Hovestadt V, Jones DT, et al.: Melanotic tumors of the nervous system are characterized by
distinct mutational, chromosomal and epigenomic profiles. Brain Pathol. 2015, 25:202-8. 10.1111/bpa.12228
14. Wiedemann GM, Aithal C, Kraechan A, et al.: Microphthalmia-Associated Transcription Factor (MITF)
Regulates Immune Cell Migration into Melanoma. Transl Oncol. 2019, 12:350-60.
10.1016/j.tranon.2018.10.014
15. Skelton HG 3rd, Smith KJ, Barrett TL, Lupton GP, Graham JH: HMB-45 staining in benign and malignant
melanocytic lesions. A reflection of cellular activation. Am J Dermatopathol. 1991, 13:543-50.
10.1097/00000372-199113060-00004
16. Balakrishnan R, Porag R, Asif DS, Satter AM, Taufiq M, Gaddam SS: Primary intracranial melanoma with
early leptomeningeal spread: a case report and treatment options available. Case Rep Oncol Med. 2015,
2015:293802. 10.1155/2015/293802
17. Ma Y, Gui Q, Lang S: Intracranial malignant melanoma: A report of 7 cases . Oncol Lett. 2015, 10:2171-5.
10.3892/ol.2015.3537
18. Troya-Castilla M, Rocha-Romero S, Chocrón-González Y, Márquez-Rivas FJ: Primary cerebral malignant
melanoma in insular region with extracranial metastasis: case report and review literature. World J Surg
Oncol. 2016, 14:235. 10.1186/s12957-016-0965-7
19. Han CH, Brastianos PK: Genetic characterization of brain metastases in the era of targeted therapy . Front
Oncol. 2017, 7:230. 10.3389/fonc.2017.00230
20. Küsters-Vandevelde HV, Küsters B, van Engen-van Grunsven AC, Groenen PJ, Wesseling P, Blokx WA:
Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects . Brain
Pathol. 2015, 25:209-26. 10.1111/bpa.12241

2021 Tuz Zahra et al. Cureus 13(7): e16194. DOI 10.7759/cureus.16194 11 of 11

 Citation: Spinal Cord Series and Cases (2015) 1, 15003; doi:10.1038/scsandc.2015.3
© 2015 International Spinal Cord Society All rights reserved 2058-6124/15
www.nature.com/scsandc

CASE REPORT
Primary spinal melanoma of extramedullary origin: a report
of three cases and systematic review of the literature
Q-Y Liu1,2, A-M Liu3, H-G Li4 and Y-B Guan5

STUDY DESIGN: A review of the literature and three case reports.

OBJECTIVES: Primary spinal melanoma (PSM) of extramedullary origin is a rare malignant condition with limited current literature
in regards to its clinical course, magnetic resonance imaging (MRI) findings, treatment strategies and prognosis. We reported here
three cases of PSM of extramedullary origin.
SETTING: China, Guangzhou.
METHODS: We report three cases of PSM of extramedullary origin. The clinical and radiological findings of these cases were
retrospectively analyzed.
RESULTS: The three cases were all of males aged 39, 47 and 76 years, respectively. The duration of their symptoms was 3 weeks,
2 months and 11 months respectively. The extramedullary tumors were all well-defined solitary tumors and were located at C4-5,
L2-3 and T9-10, respectively. In one case, involvement of the intervertebral foramen was found. Preoperative MRI showed
hyperintense T1W signals and hypointense T2W signals in all three cases and all tumors were clinically misdiagnosed as
schwannomas. The patients received total or subtotal resection surgery without radiotherapy or chemotherapy. Patients were alive
at 18 months, 27 months and 36 months postoperative follow-up, respectively.
CONCLUSION: PSM of extramedullary origin is a rare malignant tumor that shows characteristic findings on MRI. Surgical resection
is the preferred treatment strategy.
Spinal Cord Series and Cases (2015) 1, 15003; doi:10.1038/scsandc.2015.3; published online 9 July 2015

INTRODUCTION Diagnosis of melanoma was established histopathologically. No

Primary central nervous system (CNS) melanoma is a rare
malignant condition, accounting for 1% of total CNS
melanomas.1 Primary spinal melanoma (PSM) of extramedullary
origin is an even rarer tumor; its diagnostic criteria are that there
are no melanomas in locations other than the CNS (such as in the
skin, mucosa or retina), and that melanoma is confirmed by
histopathology.1 There are few published cases of PSM of
extramedullary origin.
CASE PRESENTATIONS
Case 1
A 39-year-old male experienced 2 months of bilateral lower limb
weakness from the hip with associated numbness and a 10-day
history of ataxic gait. Neurological examination revealed high
bilateral lower limb muscle tension with 4/5 power response in
both legs and abnormal superficial sensation below T12. Magnetic
resonance imaging (MRI) examination showed an extramedullary
tumor at the T9-10 level, with measurements 1.9 cm × 0.9 cm × 1.2
cm. The well-defined mass was hyperintense on T1W images,
hypointense on T2W images and homogeneously moderate
enhancement after contrast administration (Figure 1). After
exposing the dura, an oval-shaped black tumor was shown to
be tightly adhered to the left T9 nerve root and spinal cord, and
subsequently a subtotal resection of the tumor was performed.
other melanoma foci were found after comprehensive post-
operative examinations. The patient did not receive chemother-
apy, radiotherapy or immunotherapy due to economic reasons.
After 7 months of postoperative follow-up, the patient was still
alive with improved neurological function.
Case 2
A 47-year-old male presented with an 11-month history of right
finger numbness. Neurological examinations showed upper right
limb hypoesthesia focusing on the dorsum of the right hand.
Motor strength of the right upper limb was weakened (4/5 power
response). Cervical MRI showed an extramedullary tumor at the
C4-5 level, with measurements 1.3 cm × 2.6 cm × 1.5 cm. The
tumor had spread to the right intervertebral foramen. It was
hyperintense on T1W images, hypointense on T2W images and
slightly enhanced after contrast administration. More hypointense
patchy areas were found inside the tumor on T2W images
(Figure 2). The patient underwent complete resection of the tumor
with C5 nerve preservation. After the dura was opened, a solid
black tumor growing along the right C5 nerve root was observed
adherent to the spinal cord. Histopathology confirmed the tumor
to be melanoma. No melanoma foci were discovered in any other
parts of the body after comprehensive examination. The patient
refused further postoperative radiotherapy, chemotherapy or

1
Department of Radiology, Zengcheng People’s Hospital, Zengcheng, Guangdong Province, China; 2Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen
University, Guangzhou, Guangdong Province, China; 3Division of Neurosurgery, Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou,
Guangdong Province, China; 4Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China and 5Department of
Radiology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, China.
Correspondence: Professor Q-Y Liu (liu.qingyu@163.com)
Received 5 December 2014; revised 12 January 2015; accepted 14 January 2015
 Primary spinal melanoma
Q-Y Liu et al
2
Figure 1. A 39-year-old male with PSM of extramedullary origin at
T9-10. MRI shows a hyperintense mass (arrow) on sagittal T1W
image (a), hypointense on sagittal T2W image (b) at T9-10 (arrow)
and homogeneous enhancement after contrast administration on
axial image (c).
immunotherapy, and was still alive with improved neurological
function after 76 postoperative months.
Case 3
A 76-year-old male presented with a 3-week history of lower
extremity weakness. Neurological examinations revealed 4/5
power response in the left lower extremity and 3/5 in the right
lower extremity. Sensation was also reduced below the knee.
Lumbar MRI revealed an extramedullary tumor located on the
right anterior side of the spinal cord with a well-defined margin
and measurements 1.3 cm × 1.5 cm × 5.0 cm. The tumor was
slightly hyperintense on T1W images, primarily hypointense on
T2W images and heterogeneous moderate enhancement after
contrast administration (Figure 3). The patient underwent total
resection of the tumor. After dural incision, a black-colored
extramedullary tumor was observed with abundant blood supply.
Histopathological examination revealed melanoma. No melanoma
foci were observed in other parts of the body after comprehensive
postoperative examinations. The patient refused further post-
operative radiotherapy, chemotherapy or immunotherapy. The
patient was alive with improved neurological function after 67
postoperative months.
Spinal Cord Series and Cases (2015) 15003
Figure 2. A 47-year-old male with PSM of extramedullary origin at
C4-5. MRI shows a hyperintense mass on sagittal T1W image (a),
hypointense on sagittal T2W image at C4-5 (b) and homogeneously
mild enhancement after contrast administration on axial image,
which extends to the right intervertebral foramen (c).
DISCUSSION
The origin of PSM is still unclear; it may originate from
melanoblasts accompanying the pia mater sheaths of vascular
bundles or from neuroectodermal rest cells during embryo-
genesis.2,3
A systematic retrospective analysis of all the English literature
on PSM of extramedullary origin published between 2000 and
2013 was performed. Papers were retrieved from PubMed using
‘primary melanoma’ and ‘spinal’ in ‘All fields’, ‘2000/01/01 to
2013/12/31’ in the ‘Date-Publication’ and ‘English’ in ‘Language’.
A total of 24 patients with PSM of extramedullary origin have
been summarized in a detailed table (Table 1).
This tumor can occur at any spinal segment; however, there
were slightly more cases in the cervical segments (39.3%, 11/28).
The patients were 16–82 years (mean: 47 years old) without
gender preference. The majority of tumors were solitary and only
one patient with multiple foci was reported.4 A few tumors
originated from the nerve roots or had spinal nerve root
involvement,5–9 which led to the enlargement of the intervertebral
foramen, and even spread outside the intervertebral foramen2,10
or destruction of the vertebral pedicles.8,11
Signs and symptoms of this tumor were nonspecific and
dependent on location.12 However, literature concerning the
symptomatic bilateral papilledema induced by increased intracra-
nial pressure 13 or the presence of subarachnoid hemorrhage-like
symptoms have been reported, and thus clinicians should be
aware of these rare presentations.14
© 2015 International Spinal Cord Society

Figure 3. A 76-year-old male with PSM of extramedullary origin at L2-3. MRI shows a slightly hyperintense mass on sagittal T1W image (a) and
hypointense on sagittal T2W image (b). Hematoxylin and eosin staining shows a highly cellular malignant tumor with dense deposition of
melanin granules (200 × ) (c) and immunohistochemical studies showed positivity for HMB-45 (200 × ) (d).
PSM of extramedullary origin show typical changes on MRI. It
presents with hyperintense T1W signals, hypointense T2W signals
and varying enhancements. The characteristic MRI findings may
be associated with melanin concentration and hemorrhages. The
paramagnetic effect of stable, free radicals and blood products
(methemoglobin) caused shortening of the T1 and T2 relaxation
times in melanoma, consequently producing hyperintensity on
T1W images and hypointensity on T2W images. Higher melanin
concentration was associated with higher signal intensities on
T1W images and lower signal intensities on T2W images.15 In CNS
melanoma, this typical sign was observed in less than half of the
patients;16 however, in our review of PSM of extramedullary origin,
these typical changes were observed in 95% (20/21) of patients.
Therefore, when an intraspinal extramedullary tumor shows
hyperintense T1W and hypointense T2W signaling, melanoma
should be suspected.2
Clinically, PSM of extramedullary origin may be misdiagnosed as
a neurogenic tumor (schwannoma), ependymoma, metastatic
tumor, hematoma or meningioma.3,5–7,9–11,17–19 Ninety percent of
melanomas found in the CNS are metastatic tumors.8 A thorough
physical examination is required to rule out melanoma in other
organs outside of the spinal cord, before a diagnosis of PSM can
be established. Spinal schwannoma or meningioma lacks the
characteristic signals (hyperintensity on T1W and hypointensity on
© 2015 International Spinal Cord Society
Primary spinal melanoma
Q-Y Liu et al
3
T2W) on MRI examination, even in pigmented schwannoma or
meningioma.15 Spinal extramedullary hematoma usually presents
with intense, ‘knife-like’ pain at the location of the hemorrhage
(‘coup de poignard’) and subsequently progressive paralysis below
the affected spinal level. These clinical features are different from
those of primary melanoma.20
Although the treatment of PSM of extramedullary origin has not
yet been standardized, most researchers recommend total surgical
resection. Radiotherapy (from 30 to 60 Gy; median dose: 33.5 Gy)
is effective for local control and is reserved for palliation of
symptoms due to spinal cord compression or as an adjuvant to
laminectomy.5,6,10,11,17,18,21 Melanoma is also refractory to most
systemic chemotherapies. Currently, it has not been confirmed
whether postoperative radiotherapy or chemotherapy (such as
interferon, methotrexate and temozolomide) has a significant role
in overall survival time.5,6,10,11,17,18,21 Although immunotherapy is
the current paradigm shift in management of melanoma, the role
of immunotherapy in these rare and particular cases have not yet
been documented in the literature.
Metastasis was observed in the patients at diagnosis or after
surgery and the locations included the brain, lung, bone, systemic
metastasis or the intraspinal metastasis.3,8,17,21,22 Of the total
27 cases, only 2 cases had recurrence records.14,17 The survival
time of PSM was between 2 weeks and 17 years (median time:
Spinal Cord Series and Cases (2015) 15003
 4

Table 1. Primary extramedullary malignant melanoma: review of the literature from 2000 to 2013

Authors Age (yr)/ Duration Level Preoperative diagnosis Treatment Recurrence/metastases Follow-up T1W/T2W/Enh on MRI
gender

Schneider et al.22 65/M 10 yr L2-4 NS Excision without Rad or Ch NS/vertebral 1 mo, died NS/NS/Enh
Sanz-Trelles et al.23 26/M 3 mo L3 NS Total excision without Ch or No/No 24 mo, alive NS
Rad
Naing et al.5 42/F NS L2 Nerve sheath tumors Subtotal excision with Rad No/No NS NS/NS/Enh

Spinal Cord Series and Cases (2015) 15003

and Ch
Freudenstein et al.17 54/F 8 yr T10-12 Ependymoma Subtotal excision with Rad Yes/intraspinal 6 yr, died Hyper-/hypo-/Enh
and Ch
Kwon et al.6 45/F 4 yr C6-7 Neurogenic tumor Total excision with Rad No/NS 8 mo, alive Hyper-/hypo-/Enh
Montinaro et al.14 57/F NS L1-2 NS Total excision Yes/NS 3 mo, alive Hyper-/hyper-/Enh
Kouninet al.13 41/F 9 mo C2–4 NS Total excision without Rad NS/NS 3 mo, alive Hyper-/hypo-/NS
Mekni et al.24 34/M NS T6-8 NS Subtotal excision NS/NS 3 mo, alive Hyper-/hypo-/Enh
Unal et al.16 37/F 4 mo T7 NS Total excision with Ch NS/NS 6 mo, alive Hyper-/hypo-/Enh
Kanatas et al.10 76/F 8 mo C6-7 Neurofibroma Subtotal excision with Rad NS/NS 6 mo, alive NS/NS/Enh
Vij et al.25 40/M 6 mo C1-2 NS Excision without Rad or Ch No/No 1 yr, alive Hyper-/hypo-/Enh
Kim et al.12 34/F 12 mo T4 NS Total excision without Rad No/No 3 yr, alive Hyper-/hypo-/Enh
or Ch
Q-Y Liu et al
Primary spinal melanoma

Jo et al.11 68/F 5 da T7-8 Metastatic tumor Subtotal excision with Rad NS/NS 6 mo, died Hyper-/hypo-/Enh
and Ch
18
Lee et al. 39/M 11 mo C1-6 Subdural hematoma Total excision with Rad No/NS 17 mo, alive Hyper-/hypo-/Enh
and Ch
Lee et al.7 71/F 12 mo C6-7 Neurofibroma or Subtotal excision NS/NS NS Hyper-/hypo-/Enh
schwannoma
8
Ganiüsmen et al. 49/F 2 yr L3 NS Total excision, with Rad No/ lung and S1 4 yr, alive Hyper-/hyper-/NS
and Ch bone
Jaiswal et al.1 16/M NS C1–5 NS Total excision NS/NS 4 mo, alive Hyper-/hypo-/Enh
Jaiswal et al.1 40/M NS C1–2 NS Total excision NS/NS 4 mo, alive Hyper-/hypo-/Enh
Katalinic et al.21 30/M NS T7-9 NS Total excision without Rad No/systemetic 17 yr, died NS
Yan et al.2 44/F 3 mo L2 − 4 NS Total excision, without Rad NS/NS NS Hyper-/hypo-/NS
Yu et al.3 48/M 6 mo C2-6 Melanoma Subtotal excision NS/ brain 2 mo, died Hyper-/hypo-/Enh
Cicuendez et al.19 82/F 1 mo L2 Schwannoma or meningioma Subtotal excision with Rad NS/NS 2 mo, died Hyper-/hypo-/Enh
Huang et al.4 24/M 1 mo Thoracic and cervical NS Total excision of thoracic NS/NS 2 wk, alive Hyper/iso to hypo-/
level lesion Enh
Sinha et al.9 55/M NS L4 Neurofibroma Total excision No/No 38 mo, alive NS
Liu et al. 39/M 2 mo T9-10 Schwannoma Subtotal excision without Rad No /intraspinal 18 mo, alive Hyper-/hypo-/Enh
or Ch
Liu et al. 47/M 11 mo C4-5 Schwannoma Total excision without Rad No/No 36 mo, alive Hyper-/hypo-/Enh
or Ch
Liu et al. 76/M 3 wk L2-3 Schwannoma Subtotal excision without No/No 27 mo, alive Hyper-/hypo-/Enh
Rad or Ch
Abbreviations: Ch, chemotherapy; da, days; Enh, enhancement; F, female; Hyper-, hyperintense; hypo-, hypointense; M, male; mo, months; NS, not stated; Rad, radiotherapy; wk, weeks; yr, years.

© 2015 International Spinal Cord Society


7 months). Six patients died during postoperative follow-up.
Because of limited follow-up data, the exact survival rate is still
unclear and a comparison of prognosis cannot be performed
between patients with postoperative radiotherapy and those with
postoperative chemotherapy.
CONCLUSION
In summary, PSM of extramedullary origin is very rare. The
preoperative diagnosis is primarily based on typical MRI presenta-
tions. The primary treatment strategy for this tumor is surgery, and
additional postoperative radiotherapy or chemotherapy may be
implemented if necessary.
ACKNOWLEDGEMENTS
We appreciate the help offered by Mr Charles Qian Wang (Prince of Wales Hospital,
University of New South Wales, Sydney, Australia) for English editing.
COMPETING INTERESTS
The authors declare no conflict of interest.
REFERENCES
1 Jaiswal S, Vij M, Tungria A, Jaiswal AK, Srivastava AK, Behari S. Primary melanocytic
tumors of the central nervous system: a neuroradiological and clinicopathological
study of five cases and brief review of literature. Neurol India 2011; 59: 413–419.
2 Yan L, Chang Z, Liu Y, He BR, Hao DJ. Primary spinal melanoma: a case report and
literature review. Chin Med J (Engl) 2012; 125: 4138–4141.
3 Yu J, Zhao DD, Chen S, Zhang JM, Xu J. Primary melanoma of the cervical spine
with cerebral metastases: case report and review of the literature. J Int Med Res
2012; 40: 1207–1215.
4 Huang X, Pan X, Huang H, Zhan R. Multiple spinal cord melanoma: case report
with emphasis on the difficult preoperative diagnosis. Turk Neurosurg 2013; 23:
534–538.
5 Naing A, Messina JL, Vrionis FR, Daud AI. Uncommon manifestations of common
malignancies: case 3. Malignant melanoma arising from a spinal nerve root. J Clin
Oncol 2004; 22: 3194–3195.
6 Kwon SC, Rhim SC, Lee DH, Roh SW, Kang SK. Primary malignant melanoma of the
cervical spinal nerve root. Yonsei Med J 2004; 45: 345–348.
7 Lee NK, Lee BH, Hwang YJ, Sohn MJ, Chang S, Kim YH et al. Findings from CT, MRI,
and PET/CT of a primary malignant melanoma arising in a spinal nerve root. Eur
Spine J 2010; 19: S174–S178.
© 2015 International Spinal Cord Society
Primary spinal melanoma
Q-Y Liu et al
5
8 Ganiüsmen O, Özer FD, Mete M, Özdemir N, Bayol Ü. Slow progression and
benign course of a primary malign melanoma of a lumbar nerve root. Clin Neurol
Neurosurg 2012; 114: 166–168.
9 Sinha R, Rizvi TH, Chakraborti S, Ballal CK, Kumar A. Primary melanoma of the
spinal cord: a case report. J Clin Diagn Res 2013; 7: 1148–1149.
10 Kanatas AN, Bullock MD, Pal D, Chakrabarty A, Chumas P. Intradural extra-
medullary primary malignant melanoma radiographically mimicking a neurofi-
broma. Br J Neurosurg 2007; 21: 39–40.
11 Jo KW, Kim SR, Kim SD, Park IS. Primary thoracic epidural melanoma: a case report.
Asian Spine J 2010; 4: 48–51.
12 Kim MS, Yoon do H, Shin DA. Primary spinal cord melanoma. J Korean Neurosurg
Soc 2010; 48: 157–161.
13 Kounin GK, Romansky KV, Traykov LD, Shotekov PM, Stoilova DZ. Primary spinal
melanoma with bilateral papilledema. Clin Neurol Neurosurg 2005; 107: 525–527.
14 Montinaro A, Cantisani P, Punzi F, D'Agostino A. Cauda equina melanoma pre-
senting with subarachnoid hemorrhage. A case report. J Neurosurg Sci 2004; 48:
139–141.
15 Smith AB, Rushing EJ, Smirniotopoulos JG. Pigmented lesions of the central
nervous system: radiologic-pathologic correlation. Radiographics 2009; 29:
1503–1524.
16 Unal B, Castillo M. MRI features of a primary thoracic epidural melanoma: a
case report. Clin Imaging 2007; 31: 273–275.
17 Freudenstein D, Wagner A, Bornemann A, Ernemann U, Bauer T, Duffner F. Pri-
mary melanocytic lesions of the CNS: report of five cases. Zentralbl Neurochi 2004;
65: 146–153.
18 Lee CH, Moon KY, Chung CK, Kim HJ, Chang KH, Park SH et al. Primary intradural
extramedullary melanoma of the cervical spinal cord: case report. Spine (Phila Pa
1976) 2010; 35: E303–E307.
19 Cicuendez M, Paredes I, Munarriz PM, Hilario A, Cabello A, Lagares A. Primary
melanoma of the cauda equina: Case report and review of the literature. Neu-
rocirugia (Astur) 2012; 23: 112–115.
20 Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a literature survey with
meta-analysis of 613 patients. Neurosurg Rev 2003; 26: 1–49.
21 Katalinic D, Anic B, Stern-Padovan R, Mayer M, Sentic M, Cikes N et al. Low back
pain as the presenting sign in a patient with primary extradural melanoma of the
thoracic spine—a metastatic disease 17 years after complete surgical resection.
World J Surg Oncol 2011; 9: 150.
22 Schneider F, Putzier M. Primary leptomeningeal melanoma. Spine (Phila Pa 1976)
2002; 27: E545–E547.
23 Sanz-Trelles A, Arranz-Salas IM, Valenzuela-Serrano MI. Melanoma arising in and
limited to a spinal nerve root of the cauda equina. Histopathology 2003; 43:
603–604.
24 Mekni A, Braham E, Nouira K, Ben Hammouda K, Bellil K, Haouet S et al. Primary
central nervous system malignant melanoma: report of 5 cases. Pathologica 2007;
99: 71–75.
25 Vij M, Jaiswal S, Jaiswal AK, Behari S. Primary spinal melanoma of the cervical
leptomeninges: report of a case with brief review of literature. Neurol India 2010;
58: 781–783.
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