Open Access

Intracranial amelanotic melanoma: a case report with literature review

World Journal of Surgical Oncology201513:182

https://doi.org/10.1186/s12957-015-0600-z

Received: 29 December 2014

Accepted: 28 April 2015

Published: 12 May 2015

Abstract

Background

The incidence of primary central nervous system (CNS) melanocytic neoplasms is relatively low comparing to systemic ones. The performance of the tumor is variable. With poor clinical experience, the diagnosis and treatment of such tumors present to be a challenge. Amelanotic melanoma is an especially rare subtype. Only several cases have been reported.

Case presentation

We report a case of intracranial amelanotic melanoma. Preoperative assessment revealed progressive right frontal mass. The patient underwent tumor resection. The pathologic analysis reported amelanotic melanoma of intermediate grade. The further examination of the whole brain and body was negative. The familial history was also negative. The patient recovered uneventfully and went on for radiotherapy and chemotherapy. After a follow-up period of 5 months, the patient was tumor-free.

Conclusions

This is the second report about primary CNS amelanotic melanoma. We summarized characteristics of the primary CNS melanocytic lesions and amelanotic melanoma with review of the literature and review of cases of our department.

Keywords

Central nervous systemIntracranialPrimaryMelanocytic lesionAmelanotic melanoma

Background

Primary melanocytic neoplasms of the central nervous system (CNS) belong to the tumors of the meninges. The incidence is less than 0.1%. Some may relate to certain neurocutaneous syndrome. The tumor can affect the entire CNS, with miscellaneous performances. The diagnosis is always difficult before the pathology result is available. And due to the potential of malignant transformation and dissemination, the identification of the original loci is even harder. So the clinical diagnosis and treatment must base on an overall evaluation of a patient. Primary amelanotic melanoma is a special subtype of the melanocytic neoplasm, which is especially rare. We want to share our experiences of primary CNS melanocytic neoplasms and amelanotic melanoma through our cases with review of the literature.

Case presentation

Medical history

A 64-year-old man presented to our department in December 2013 for progressive right frontal mass with dull aching for 9 months. His medical history was unremarkable except for 2 years of hypertension. The familial history was negative, with no neurocutaneous system disorders of the first grade relatives.

Clinical examination

The vital signs were stable. A mass at the right frontal region could be palpated, about 5 cm in diameter, hard, fixed, with no obviously red, swollen, or tender of the superficial scalp.

Imaging studies

Cranial CT scan showed an mixed iso-/hyperdensity mass in the right frontal cranial bone, about 60 to 198 Hu, measuring 34 × 21 mm, with clear margin. The peripheral bone appeared destructive absorption. The MR was contraindicated for metal implant (Figure 1).
Figure 1

Preoperative CT scan of the patient. The lesion locates in the right frontal bone, isointense on CT scan, with prominent bone destruction. (a) CT scan of the soft tissue. (b) CT scan of the cranial bone.

Surgery, pathologic result, and postoperative course

The patient underwent total tumor resection through right frontal approach on 24 December, 2013. The tumor eroded both the external and internal lamina of the cranial bone. The tumor was solid, soft, tender, pale white, rich blood supplied, and was adhesive to the underlying dura mater. The dura mater was yet intact, sparing the parenchyma of the cortex. The intraoperative rapid frost pathologic examination revealed malignant changes, and so after tumor resection, the adjacent dura mater was removed as well which was reconstructed with self aponeurosis. The peripheral bone was resected to the negative zone. The excision margin was about 2 cm.

The pathologic examination reported amelanotic melanoma of intermediate grade, with positive of HMB45, MelanA (sparsely), S-100, Vimentin, CD99, SMA (sparsely), and CD34, and negative of CK, EMA, CEA, CK5/6, CK8/18, TTF-1, SYN, CD56, CgA, Desmin, MyoD1, TFE3, PAS, and PR. The Ki-67 was 20% to 30% (±) (Figure 2).
Figure 2

Pathologic results. (a) Pathology slice (hematoxylin-eosin stain, original magnification ×100) of the tumor. Nests of intermediate-grade tumor cells with intervening stroma can be seen. The tumor cells show clear to eosinophilic cytoplasm, with no obvious pigment. (b) Higher magnification (hematoxylin-eosin stain, original magnification ×400) of the tumor, showing prominent nuclear mitosis and atypia. (c) Higher magnification (original magnification ×400) of the tumor, showing HMB45 positive. (d) Higher magnification (original magnification ×400) of the tumor, showing S-100 positive. (e) Higher magnification (original magnification ×400) of the tumor, showing Vimentin-positive. (f) Higher magnification (original magnification ×400) of the tumor, showing Ki-67 index, was 20% to 30%.

The further examination includes CT scan of the chest, abdominal, and the pelvic region and the PET scan of the whole brain and body, which were all negative.

The patient was discharged 3 days after the operation with no complications and went on for adjuvant radiotherapy and chemotherapy (concomitant stereotactic radiosurgery + ipilimumab). For more than 5 months of follow-up, the patient recovers well with no recurrence or related sequelae.

Review of cases and literature

We summarized the CNS melanocytic lesions of our neurosurgery department since 2008. Then we used the search engine of PubMed with keywords of melanoma or melanomatosis or melanocytoma or melanocytosis, and CNS and primary and further searched with keywords of CNS or brain or cranial or spinal, and amelanotic.

Thirty-two cases of CNS melanocytic lesions of our department were defined since 2008. Forty-three English reports of CNS melanocytic lesions and 14 reports about CNS amelanotic melanoma were searched. The details were summarized in the tables (Tables 1, 2, and 3).
Table 1

Summary of CNS melanocytic lesions of our neurosurgery department since 2008

Case

Gender

Age (yr.)

Location

Pathology diagnosis

Preoperative differentiation a

1

M

46

Left temporal

Intermediate-grade melanocytic tumor

-

2

M

11

Right temporal

Malignant melanoma

-

3

M

45

Right frontal

Malignant melanoma

Metastasis? Lymphoma?

4

F

26

Right parasellar

Malignant melanoma

Schwannoma?

5

F

52

Left frontal

Metastatic melanoma

-

6

M

43

Right temporal

Meningeal melanomatosis

Metastasis? Pleomorphic xanthoastrocytoma?

7

M

47

Right CPA

Meningeal melanomatosis

Epidermoid cyst? Cavernous hemangioma?

8

M

24

Right lateral ventricle

Amelanotic melanoma?

-

9

F

19

Left parietal

Melanocytoma

Meningioma?

10

F

21

Right frontal, para-falx

Recurrent melanocytoma, with subarachnoid dissemination

Recurrent melanocytoma

11

M

38

Right petrosal

Meningeal melanomatosis

Schwannoma?

12

M

61

Multiple

Melanocytoma with meningeal melanomatosis

Melanoma? Metastasis?

13

M

20

Left temporal

Malignant melanoma

-

14

M

24

Right cerebellar

Malignant melanoma

Cyst?

15

M

47

Foreman magnum

Malignant melanoma, with bone invasion

Meningioma? Melanoma?

16

M

47

Left middle fossa

Malignant melanoma

Hemangiopericytoma? Meningioma? Melanoma?

17

M

45

Intradural extramedullary, C2-T1

Melanocytoma

Melanoma? Meningioma?

18

M

31

Right cavernous sinus

Melanocytoma

Melanoma? Cavernous hemangioma? Aneurysm?

19

M

46

Right middle fossa

Malignant melanoma, with bone and dura invasion

Meningioma?

20

M

20

Left pons

Malignant melanoma

Glioma? Meningioma?

21

F

41

Multiple, T6-L1

Melanocytoma

Neurofibrosis?

22

F

28

Right parietal occipital

Malignant melanoma, with subarachnoid dissemination

-

23

F

66

Left frontal

Malignant melanoma

-

24

M

27

Right interspinous foramen, C6

Melanocytoma

Melanoma?

25

M

39

Foramen magnum - C2

Melanocytoma

Lipoma?

26

M

36

Right frontal

Melanocytoma, with subarachnoid dissemination and parenchyma invasion

Melanoma? Lymphoma?

27

M

49

Right cerebellar tentorium

Meningeal melanomatosis

Meningioma?

28

M

17

Left parasallar - CPA

Melanocytoma

Epidermoid cyst?

29

M

26

Medulla

Intermediate grade melanocytic tumor

-

30

M

13

Right cerebellar tentorium

Malignant melanoma

Meningioma? Hemangiopericytoma?

31

M

47

Left temporal

Malignant melanoma

-

32

M

64

Right frontal bone

Amelanotic melanoma, with bone invasion

Eosinophilic granuloma? Giant cell osteoma? Metastasis?

M, male; F, female, yr., years old. aWith no clear preoperative diagnosis.

Table 2

Review of the English literature of CNS melanocytic lesions

Author

Year

Nb

Primary/metastatic a

Diagnosis

Other

Foit et al.

2013

1

Primary

Melanocytoma

-

Lee et al.

2013

1

Primary

Meningeal melanomatosis

-

Schneider et al.

2013

1

Primary

Malignant melanoma

-

Reddy et al.

2012

1

-

Melanocytoma

-

Sutton et al.

2011

1

-

Leptomeningeal melanocytosis

The patient was suspected to represent a case of former fruste neurocutaneous melanosis.

Brunsvig et al.

 

1

-

Meningeal melanocytosis

-

Vij et al.

2010

1

Primary

Melanoma

-

Perrini et al.

2010

1

Primary

Malignant melanoma

-

Zadro et al.

2010

1

Primary

Diffuse meningeal melanomatosis

-

Nishihara et al.

2009

1

Primary

Malignant melanoma

-

Navas et al.

2009

1

-

Meningeal melanocytoma

Associated with a congenital nevus of Ota

Holfort et al.

2009

16

Metastatic

Melanoma

Out of review of primary uveal melanoma 2365 patients

Mathai et al.

2008

1

-

Intermediate grade meningeal melanocytoma

-

Tandon et al.

2008

1

Primary

Melanocytoma

-

Levidou et al.

2007

2

Unknown primary site

Leptomeningeal melanoma

-

Cajaiba et al.

2008

2

Primary

Neurocutaneous melanosis with CNS melanocytoma

Disseminated to the peritoneal surface by ventriculo-peritoneal (V-P) shunt system

Mekni et al.

2007

5

Primary

Malignant melanoma

-

Denaro et al.

2007

1

Primary

Melanoma

-

Bookland et al.

2007

1

Primary

Malignant melanoma

-

Kiecker et al.

2007

1

Primary

Neurocutaneous melanosis with meningeal melanoma

-

Oluigbo et al.

2006

1

Primary

Malignant melanoma

-

Chen

2003

1

-

Meningeal melanocytoma

-

Classen et al.

2002

1

-

Melanocytoma

-

Rivers et al.

2001

1

Primary

Dural melanoma

In association with ocular melanosis and multiple cutaneous blue nevi

Greco Crasto et al.

2001

1

Primary

Melanoma

-

Whinney et al.

2001

1

Primary

Malignant melanoma

-

Kobayashi et al.

2001

1

-

Malignant melanoma

-

Fathallah-Shaykh et al.

1996

1

Primary

Leptomeningeal melanoma

-

Eaves et al.

1995

1

Primary

Melanoma without diffuse leptomeningeal involvement

A variant of neurocutaneous melanosis

Rubino et al.

1993

1

Primary

Melanoma

-

Drake et al.

1993

8

Primary

Malignant melanoma of the leptomeninges

-

Singhal et al.

1991

1

Primary

Melanoma

-

Fish et al.

1990

1

Primary

Melanoma

-

Salisbury et al.

1989

1

Primary

Malignant melanoma

In association with a giant congenital melanocytic naevus of ‘bathing trunk’ distribution

Macfarlane et al.

1989

1

Primary

Malignant melanoma of the dura mater

-

Iglesias-Rozas et al.

1989

1

-

Disseminated melanomatosis of the CNS and other organs

-

Larson et al.

1987

5

Primary

Melanoma

-

Tamura et al.

1981

1

Primary

Leptomeningeal malignant melanoma

Originated from the basal aspect of the brain. The tumor showed not only spinal meningeal dissemination but also infiltration into the petrous bone and along the trigeminal nerve till it reached the submucosal tissue of epipharynx.

Pasquier et al.

1978

1

primary

Melanoma

With multiple metastases in the liver

Hayward

1976

27

20 Metastatic, 6 Primary

Malignant melanoma

-

Kaplan et al.

1975

1

Primary

Neurocutaneous melanosis with malignant leptomeningeal melanoma

-

Enriquez et al.

1973

1

Primary

Malignant melanoma

Pineal involvement in a patient with nevus of ota and multiple pigmented skin nevi.

Bergdahl et al.

1972

10

Primary

Malignant melanoma

-

CNS, central nervous system, the involved cases are all of the CNS, either intracranial or intraspinal; Nb, number of reported cases. aSome cases have no clear evidence to be defined as primary or metastatic tumor.

Table 3

Review of the literature of CNS amelanotic melanoma

Author

Year

Nb

Primary/metastatic a

Diagnosis

Other b

Schulz et al. [6]

2012

1

Primary

Malignant amelanotic melanomas

(in German)

Combined multiple intracranial and intraspinal primary malignant amelanotic melanomas

Cemil et al. [7]

2008

1

Metastatic

Amelanotic melanoma

-

Karakis et al. [8]

2007

1

Metastatic

Amelanotic melanoma

-

Jacob et al. [9]

2006

1

-

Amelanotic melanoma?

-

Li et al. [10]

2004

1

-

Amelanotic melanoma?

(in Chinese)

Ogawa et al. [11]

2003

1

Metastatic

Amelanotic melanoma

-

Shields et al. [12]

2002

1

Metastatic

Amelanotic melanoma

-

Isiklar et al. [13]

1995

16

Metastatic

Amelanotic melanoma

-

Schadendorf et al. [14]

1993

1

-

Amelanotic malignant melanoma

-

Takahashi et al. [15]

1990

1

Metastatic

Amelanotic melanoma

(in Japanase)

Krüger et al. [16]

1987

1

Metastatic

Amelanotic melanoma

Associated with a congenital nevus of Ota

Sunada et al. [17]

1986

1

Unknown origin

Amelanotic melanoma

(in Japanase)

Out of review of primary uveal melanoma 2365 patients

Wagner et al. [18]

1981

1

-

Amelanotic melanoma

Amelanotic melanoma of the lung and brain

Schuknecht et al. [5]

1990

2

Primary

Meningeal amelanotic malignant melanoma

-

CNS, central nervous system, the involved cases are all of the CNS, either intracranial or intraspinal; Nb, number of reported cases. aSome cases have no clear evidence to be defined as primary or metastatic tumor; bliterature in languages other than English is noted.

Discussion

Primary melanocytic neoplasms of the CNS belong to the tumors of the meninges, further classified as diffuse melanocytosis, melanocytoma, malignant melanoma, and meningeal melanomatosis. The incidence is 0.06% to 0.1% of melanocytoma and 0.005/100,000 of melanoma. Other subtypes are rare. There is a slight female predisposition, with the ratio of F:M = 1.5:1. The age range of melanocytoma is 9 to 73 years, most frequently from 45 to 50 years, and of the primary nodular melanoma is 15 to 71 years, averaging 43 years. The symptoms and signs are secondary to either the local effects on the CNS parenchyma or the accompanying hydrocephalus. The rapid progress with increasing ICP resulting in irritability, vomiting, lethargy, seizures, and so on may suggest malignant transformation. The diagnosis of melanocytic lesions relies on the histopathological examination. Most benign and malignant melanocytic lesions display melanin pigment distributed within tumor cells, tumor stroma, and the cytoplasm of tumoral macrophages (melanophages). Tumor with CNS invasion or elevated mitotic activity is classified as intermediate grade melanocytic neoplasms. Malignant melanoma is more pleomorphic, has more anaplastic nuclei, higher cell density, and unequivocal invasion or coagulative necrosis. Rare melanocytomas and occasional primary melanomas will not demonstrate melanin pigment, complying with ‘amelanotic’ Amelanotic melanoma may arise from normal melanoma with amelanotic transformation or detergent of the tumor cell. Histopathological and immunohistochemistry examinations are highly sensitive to amelanotic melanoma. The neuroimaging performance depends on the content of melanin. Isiklar et al. [1] classified the MR performance into four groups: a) The melanotic group, with hyperintense on T1 and hypointense on T2. b) The amelanotic group, with iso-/hypointense on T1 and iso-/hyperintense on T2. c) The mixed group, suiting neither the two criteria. d) The hemorrhagic group, with characteristics of intra-/peri-tumoral hemorrhage. Gaviani et al. [2] reported that the T1 signal has positive correlation with the content of melanin, while T2 signal has no such correlation but is more sensitive to tiny loci.

Early in 1980s, Willis et al. pointed out that the diagnosis of ‘primary’ has to meet three critical conditions: a) The skin or eyeballs are negative of melanoma. b) The skin or eyeballs have no history of melanoma resection. c) The internal organs are negative of metastasis of melanoma. Savitz [3] thought that the systemic melanocytic lesions are very likely to metastases to CNS while the primary loci are quite indolent. Winkelman et al. [4] reported that 44% of all melanocytic lesions have CNS metastasis at autopsy, so that the ‘primary’ can only be confirmed after autopsy. So every melanocytic neoplasm may be a systemic disease, and the ‘primary CNS melanocytic lesion’ is just a subtype with CNS as the single manifestation clinically. There are approximately more than 60 papers describing primary CNS melanocytic lesions, with about 40 are in English, dated from 1972 to 2013. The number of cases ranged from one to ten. The symptoms are various according to the location of the tumor and so are the neuroimaging performance relating to the content of the melanin, as mentioned before. About 14 papers referred to CNS amelanotic melanoma, from 1981 to 2012. Most are case reports, including two primary intraspinal and two primary meningeal amelanotic melanoma, 22 intracerebral metastasis, one intraventricular metastasis, and three cases with no details. Schuknecht et al. [5] reported two primary meningeal amelanotic melanoma in 1990, serving as the only paper describing primary CNS amelanotic melanoma. There are totally 32 primary or metastatic CNS melanocytic lesions of our department since 2008. The cases diagnosed earlier are not included because of the controversial diagnosis criterion before the 2007 WHO classification which are widely adopted. The location involves all the CNS, from supratentorial to intraspinal region. Due to the unspecific resemblance, there were only few cases which were diagnosed before surgery, and the differentiations were quite variable. The most common differentiations are tumors of the meninges, which belong to the same group of the melanocytic lesions, such as meningioma and the mesenchymal tumors. The hematopoietic neoplasms, cavernous hemangioma, and even the cystic lesions are also involved especially when there are hemorrhage, cystic changes, or necrosis, and so on. One of them was suspected as amelanotic melanoma. Our case is the second one with definite diagnosis of amelanotic melanoma. The clinical characteristics of amelanotic melanoma are similar to other melanocytic lesions, with the neuroimaging performance as the major difference. Also, during the operation, the amelanotic melanoma appears more pale white, and the microscopic examination reviews the lacking of melanin. As the overall examinations were all negative, the primary intracranial amelanotic melanoma was confirmed.

The prognosis of amelanotic melanoma is not quite different from other CNS melanoma. Melanocytoma lacks anaplastic features, but a few undergo local recurrences. Intermediate grade melanocytic tumors typically invade the CNS. A rare example of malignant transformation of a melanocytoma has been reported. Malignant melanoma is highly aggressive and radioresistant, has poor prognosis, and prone to metastasize. The prognosis of diffuse melanosis is poor even in the absence of histologic malignancy. The prognosis of the primary CNS melanocytic lesions appears to be better than metastatic examples. For our case of primary intracranial amelanotic melanoma, total resection was achieved as well as excessive removal of invaded cranial bone and adjacent meninges. The experience of postoperative adjuvant therapy is quite poor. We adopted the radiotherapy and chemotherapy regimen of concomitant stereotactic radiosurgery + ipilimumab, referring to the NCCN guidelines for melanoma (2.2015 version). With adjuvant radiotherapy and chemotherapy, the patient is tumor-free 5 months later and is still under follow-up.

Conclusions

CNS amelanotic melanoma is quite rare. The clinical characteristics are similar to other melanocytic lesions, with the neuroimaging performance as the major difference. The prognosis of amelanotic melanoma is not quite different from other CNS melanoma and appears to be better than the metastatic cases, particularly if localized and complete resection is possible.

Consent

Written informed consent was obtained from the patient for the publication of this case presentation and accompanying images. A copy of the written consent is available for the review by the Editor of this journal.

Declarations

Acknowledgements

This work was supported by the Vascular and Gerontic Tumor Group of the Neurosurgery Department, the Radioimaging Department, and the Neuro-pathology Department of Beijing Tiantan Hospital.

Authors’ Affiliations

(1)
Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor

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© Ma et al.; licensee BioMed Central. 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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