Transition from meningeal melanocytoma to primary cerebral melanoma

Case report

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✓ The authors describe the first case of an intracranial transition of a melanocytoma into a primary malignant melanoma within a short time. A 37-year-old woman presented with progressive brainstem syndrome due to a tumor, originally diagnosed and treated 12 years earlier, that extended from the petroclival area to the anterior craniocervical junction. The histological workup following subtotal tumor resection of the initial tumor had revealed the typical features of a fibrous melanocytic meningioma without increased proliferation. Ten years after the patient had completed treatment for the melanocytic meningioma, control neuroimaging demonstrated growth of the residual tumor with compression of the brainstem. Another neurosurgical intervention revealed a dark tumor of hard consistency. At this time immunohistochemical examinations demonstrated melanocytic features (expression of vimentin, S100 protein, and melan A) of the lesion with focally increased proliferation (5% of Ki-67—positive cells) but no higher mitotic activity. Clinical signs of deterioration along with imaging-confirmed tumor progression precipitated another operation within 7 months. A neuropathological examination revealed epithelial and anaplastic changes and indicated that the MIB-1 indices were greater than 25%. Pleomorphic changes and a focal high mitotic activity led to the diagnosis of a primary cerebral malignant melanoma. The patient's later clinical course consisted of a rapid diffuse meningeal spread of the lesion throughout the entire brain and spine. Despite whole-brain and stereotactic radiation therapy as well as chemotherapy, the patient died 4 months after the last neuropathological diagnosis. Although grossly resembling a meningioma, melanocytomas lack the former's histological and immunohistochemical features. The biological behavior of a melanocytoma is variable and recurrence may happen after subtotal resection, but intracranial transition into a malignant melanoma has not been observed previously.

Abstract

✓ The authors describe the first case of an intracranial transition of a melanocytoma into a primary malignant melanoma within a short time. A 37-year-old woman presented with progressive brainstem syndrome due to a tumor, originally diagnosed and treated 12 years earlier, that extended from the petroclival area to the anterior craniocervical junction. The histological workup following subtotal tumor resection of the initial tumor had revealed the typical features of a fibrous melanocytic meningioma without increased proliferation. Ten years after the patient had completed treatment for the melanocytic meningioma, control neuroimaging demonstrated growth of the residual tumor with compression of the brainstem. Another neurosurgical intervention revealed a dark tumor of hard consistency. At this time immunohistochemical examinations demonstrated melanocytic features (expression of vimentin, S100 protein, and melan A) of the lesion with focally increased proliferation (5% of Ki-67—positive cells) but no higher mitotic activity. Clinical signs of deterioration along with imaging-confirmed tumor progression precipitated another operation within 7 months. A neuropathological examination revealed epithelial and anaplastic changes and indicated that the MIB-1 indices were greater than 25%. Pleomorphic changes and a focal high mitotic activity led to the diagnosis of a primary cerebral malignant melanoma. The patient's later clinical course consisted of a rapid diffuse meningeal spread of the lesion throughout the entire brain and spine. Despite whole-brain and stereotactic radiation therapy as well as chemotherapy, the patient died 4 months after the last neuropathological diagnosis. Although grossly resembling a meningioma, melanocytomas lack the former's histological and immunohistochemical features. The biological behavior of a melanocytoma is variable and recurrence may happen after subtotal resection, but intracranial transition into a malignant melanoma has not been observed previously.

Primary pigmented lesions of the CNS are uncommon and range from melanosis of the leptomeninges to malignant melanoma. The term “meningeal melanocytoma” was first proposed by Limas and Tio10 in 1972 to describe a lesion that exhibits the microscopic features of a meningioma but the ultrastructural and immunohistochemical characteristics of a melanocytic tumor. We describe the first case of a histologically identified melanocytoma of the cerebellopontine angle that turned into a primary malignant melanoma within a short time.

Case Report
History and Examination

This 37-year-old woman presented in the year 2000 with progressive brainstem syndrome resulting from a previously discovered tumor that extended from the petroclival area to the anterior craniocervical junction. In 1988 she had undergone surgery during which, according to the pathological report, a “fibrous, melanocytic meningioma” in that region was subtotally resected. Detection of the Ki-67 antigen was not a routine diagnostic procedure at that time and, thus, in 2002 we performed an immunohistochemical analysis of the original specimen. Our analysis revealed a low level of proliferation according to Ki-67 staining (3% of cells stained with Ki-67) (Fig. 1 left). Repeated MR imaging examinations did not reveal any sign of tumor progression until 2000, when compression of the brainstem was observed.

Fig. 1.
Fig. 1.

Photomicrographs showing sections of the tumor obtained at different times. A Ki-67 immunohistochemical examination of the specimen excised in 1988 showed that 3% of the cells stained positively for Ki-67; in 2001 the percentage of Ki-67—positive cells was 5% (center) and in 2002 it was 25% (right). Original magnifications × 125 (A); × 40 (B and C).

Operations and Pathological Findings

Subtotal removal of a hard dark tumor was achieved in 2001. Histological and immunohistochemical examinations revealed the typical features of a melanocytoma (expression of vimentin, HMB-45, S100 protein, and melan A) with increased proliferation (5% of cells stained with Ki-67) but only scant mitotic activity and absent necrosis (Fig. 1 center). The sparse amount of cells was enhanced with melanin-specific stains.

Clinical deterioration as well as neuroimaging evidence of tumor progression led to another operation within 7 months. Neuropathological examinations revealed epithelial and anaplastic changes and MIB-1 indices greater than 25% (Fig. 1). The immunohistochemical analysis demonstrated similar results, but the lesion's epitheloid appearance, pleomorphic changes, high nucleus/cytoplasm ratio with vacuoles, and focal high mitotic activity led to the diagnosis of a primary cerebral malignant melanoma.

Postoperative Course

The patient's postoperative clinical course exhibited a rapid diffuse meningeal spread of the tumor throughout the entire brain and spine. Despite whole-brain (40.8 Gy) radiation therapy as well as chemotherapy (Temozolomide 200 mg/m2), the patient died 4 months after the last operation. Permission to perform an autopsy was denied.

Discussion

Pigmented cells are normally found in the leptomeninges and, according to Virchow,23 were first described by Valenti. Primary malignant melanomas have long been known to occur in the CNS. Most reported lesions have occurred either in the spinal canal or the posterior fossa because of the higher concentrations of melanocytes in the leptomeninges at the anterior and lateral surfaces of the spinal cord and ventrolateral to the medulla oblongata. In 1940, however, Ray and Foot15 described two cases of leptomeningeal melanotic tumors that followed a benign course. These tumors were once referred to as melanotic, melanoblastic, or pigmented meningiomas9,17 but ultrastructural studies have shown the melanocytic nature of these lesions.15 It is assumed that melanocytoma of the dura mater represents an area of meningeal melanocytosis that has undergone a nodular neoplastic proliferation.1,8

Histologically, the meninges-based neoplasms are characterized by interlacing fascicles of spindle cells, with a fusiform or polygonal appearance and foci of epitheloid differentiation. There is abundant melanin deposition. Rare mitoses can be seen, but necrosis, hemorrhage, and pleomorphism are very unusual. Immunohistochemical analysis as a means to differentiate between melanocytomas and melanomas remains difficult. Both lesions stain positively for S100 protein and HMB-45. Melanocytomas can exhibit vimentin but are negative for epithelial membrane antigen, the presence of the latter being typical for meningiomas.4,5,8,13

Brat and colleagues2 classified melanocytic lesions of the CNS with respect to focal mass lesions as low grade (melanocytomas) and high grade (melanoma). They placed a minority of lesions in an intermediate category because these tumors displayed increased mitotic activity and hypercellularity but not to the degree that one should categorize them as high-grade lesions. All groups were separate histological entities and transformation of a low-grade melanocytoma or an intermediate melanocytoma into a high-grade melanoma with subsequent leptomeningeal metastasis has not been described.

Several reports contain descriptions of an optic disc melanoma that develops several years after a melanocytoma has been diagnosed.11,18,19 Two cases of malignant transformation of spinal melanocytomas have been reported in the literature but the histological details are missing. A metastasizing spinal melanocytoma has been described in another patient, which is not an uncommon feature in this type of tumor entity;6,7 however, intracranial transformation of a melanocytoma with subsequent leptomeningeal spread has never been reported.

The appearance of melanocytomas on neuroimaging studies is well described.3 On MR images these lesions usually appear isointense on T1-weighted images and display homogeneous enhancement after Gd administration. Melanocytomas share some features of meningiomas, namely, attachment to the dura mater and, occasionally, local brain invasion.4 Their appearance on computerized tomography scans is often one of a dura-based iso- to high-density mass that enhances homogeneously.

Melanomas differ in that they often display a heterogeneous signal as a result of hemorrhage within the tumor. In contrast to a schwannoma, for example, a melanoma appears hyperintense on a T1-weighted image (without Gd) and hypointense on a T2-weighted image.24 In this and other reported cases, melanomas of the cerebellopontine angle have mimicked schwannomas by appearing hypointense on T1-weighted images and demonstrating enhancement following a Gd injection (Fig. 2).22

Fig. 2.
Fig. 2.

Axial Gd-enhanced T1-weighted MR images demonstrating the remnant of “melanocytic meningioma” in 1990 (upper left), a lesion bearing the histological diagnosis of “melanocytoma” in 2000 (upper right), a lesion with the histological diagnosis of “primary malignant melanoma” in 2001 (lower left), and leptomeningeal dissemination of the lesion in 2002 (lower right).

Because intracranial melanocytomas behave biologically like meningiomas, surgery is performed with the goal of total resection.5 Tumor recurrence has been reported, but the finding of malignant transformation at some point in the tumor's evolution is unique within the literature.4,13 The distinction between primary and metastatic melanoma is obviously of clinical importance. Although long-term survival and even “cures” have been documented, a substantial number of patients with primary melanoma of the CNS experience a malignant course of the disease due to rapid leptomeningeal spread.12,16,20,21,25 In patients harboring a melanoma that is metastasizing into the CNS the prognosis remains even more dismal. Therefore, a thorough physical examination should be performed in the presence of a cerebral melanoma to exclude the possibility of a primary cutaneous, mucosal, or ocular melanoma, although the solitary appearance attached to the leptomeninges may indicate a primary process. Due to the slow growth of melanocytomas, the use of postoperative radiation therapy must be individualized and should be reserved for those patients with symptomatic residual or recurrent tumors.14 Malignant melanomas require postoperative adjuvant radiation as well as chemotherapy, either following glioma protocols or cutaneous tumor approaches.

Although grossly resembling a meningioma, melanocytomas lack the histological and immunohistochemical features of a meningioma. The biological behavior of melanocytomas is variable and recurrence may happen after subtotal resection; however, prior to this case the transition of a meningeal melanocytoma into a primary cerebral melanoma of the brain had not been observed.

References

  • 1.

    Botticelli ARVillani MAngiari Pet al: Meningeal melanocytoma of Meckel's cave associated with ipsilateral Ota's nevus. Cancer 51:230423101983Cancer 51:

  • 2.

    Brat DJGiannini CScheithauer BWet al: Primary melanocytic neoplasms of the central nervous systems. Am J Surg Pathol 23:7457541999Am J Surg Pathol 23:

  • 3.

    Chen CJHsu YIHo YSet al: Intracranial meningeal melanocytoma: CT and MRI. Neuroradiology 39:8118141997Neuroradiology 39:

  • 4.

    Chow MClarke DBMaloney WJet al: Meningeal melanocytoma of the planum sphenoidale. Case report and review of the literature. J Neurosurg 94:8418452001J Neurosurg 94:

  • 5.

    Clarke DBLeblanc RBertrand Get al: Meningeal melanocytoma. Report of a case and a historical comparison. J Neurosurg 88:1161211998J Neurosurg 88:

  • 6.

    Cordoba ATunon TVazquez JJ: Melanocitoma meningeo. Presentacion de un caso y revision de la literature. Arch Neurobiol 52:93991989Arch Neurobiol 52:

  • 7.

    Ferracini RGardini GBrisigotti Met al: Metastasizing meningeal melanocytoma. Tumori 66:4054081980Tumori 66:

  • 8.

    Leonardi MALumenta CBStolzle Aet al: Unusual clinical presentation of a meningeal melanocytoma with seizures: case report and review of the literature. Acta Neurochir 140:6216281998Acta Neurochir 140:

  • 9.

    Lesoin FLeys DPasquier Fet al: Melanotic meningioma. Report of a case and review of the literature. Neurochirurgia 28:2052071985Neurochirurgia 28:

  • 10.

    Limas CTio FO: Meningeal melanocytoma (“melanotic meningioma”). Its melanocytic origin as revealed by electron microscopy. Cancer 30:128612941972Cancer 30:

  • 11.

    Meyer DGe JBlinder KJet al: Malignant transformation of an optic disk melanocytoma. Am J Ophthalmol 127:7107141999Am J Ophthalmol 127:

  • 12.

    Nakagawa HHayakawa TNiiyama Ket al: Long-term survival after removal of primary intracranial malignant melanoma. Case report. Acta Neurochir 101:84881989Acta Neurochir 101:

  • 13.

    O'Brien TFMoran MMiller JHet al: Meningeal melanocytoma. An uncommon diagnostic pitfall in surgical neuropathology. Arch Pathol Lab Med 119:5425461995Arch Pathol Lab Med 119:

  • 14.

    Rades DTatagiba MBrandis Aet al: Stellenwert der Strahlentherapie bei der Behandlung des meningealen Melanozytoms. Strahlenther Onkol 178:3363422002Strahlenther Onkol 178:

  • 15.

    Ray BSFoot NC: Primary melanotic tumors of the meninges: resemblance to meningiomas. Report of two cases in which operation was performed. Arch Neurol Psychiatry 44:1041171940Arch Neurol Psychiatry 44:

  • 16.

    Rodriguez y Baena RGaetani PDanova Met al: Primary solitary intracranial melanoma: case report and review of the literature. Surg Neurol 38:26371992Surg Neurol 38:

  • 17.

    Russell DSRubinstein LJ: Pathology of Tumors of the Nervous Systemed 5. London: Arnold1989792808

  • 18.

    Sharma PMSangal KMalik Pet al: Malignant transformation of optic disc melanocytoma? A clinical dilemma at presentation with a review of the literature. Ophthalmologica 216:2922952002Ophthalmologica 216:

  • 19.

    Shields JAShields CLEagle RC Jret al: Malignant melanoma associated with melanocytoma of the optic disc. Ophthalmology 97:2252301990Ophthalmology 97:

  • 20.

    Skarli SOWolf ALKristt DAet al: Melanoma arising in a cervical spinal nerve root: report of a case with a benign course and malignant features. Neurosurgery 34:5335371994Neurosurgery 34:

  • 21.

    Theunissen PSpincemaille GPannebakker Met al: Meningeal melanoma associated with nevus of Ota: case report and review. Clin Neuropathol 12:1251291993Clin Neuropathol 12:

  • 22.

    Vasdev ADavid PVillemot Det al: Apparently primary malignant melanoma of the cerebellopontine angle. One case. J Neuroradiol 17:1521561990J Neuroradiol 17:

  • 23.

    Virchow R: Pigment und diffuse Melanose der Arachnoides. Arch Pathol Anat 16:1801821859Virchow R: Pigment und diffuse Melanose der Arachnoides. Arch Pathol Anat 16:

  • 24.

    Woodruff WW JrDjang WTMcLendon REet al: Intracerebral malignant melanoma: high-field-strength MR imaging. Radiology 165:2092131987Radiology 165:

  • 25.

    Yamane KShima TOkada Yet al: Primary pineal melanoma with long-term survival: case report. Surg Neurol 42:4334371994Surg Neurol 42:

Article Information

Address reprint requests to: Florian Roser, M.D., Department of Neurosurgery, University of Tübingen, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany. email:f.roser@gmx.de.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Photomicrographs showing sections of the tumor obtained at different times. A Ki-67 immunohistochemical examination of the specimen excised in 1988 showed that 3% of the cells stained positively for Ki-67; in 2001 the percentage of Ki-67—positive cells was 5% (center) and in 2002 it was 25% (right). Original magnifications × 125 (A); × 40 (B and C).

  • View in gallery

    Axial Gd-enhanced T1-weighted MR images demonstrating the remnant of “melanocytic meningioma” in 1990 (upper left), a lesion bearing the histological diagnosis of “melanocytoma” in 2000 (upper right), a lesion with the histological diagnosis of “primary malignant melanoma” in 2001 (lower left), and leptomeningeal dissemination of the lesion in 2002 (lower right).

References

1.

Botticelli ARVillani MAngiari Pet al: Meningeal melanocytoma of Meckel's cave associated with ipsilateral Ota's nevus. Cancer 51:230423101983Cancer 51:

2.

Brat DJGiannini CScheithauer BWet al: Primary melanocytic neoplasms of the central nervous systems. Am J Surg Pathol 23:7457541999Am J Surg Pathol 23:

3.

Chen CJHsu YIHo YSet al: Intracranial meningeal melanocytoma: CT and MRI. Neuroradiology 39:8118141997Neuroradiology 39:

4.

Chow MClarke DBMaloney WJet al: Meningeal melanocytoma of the planum sphenoidale. Case report and review of the literature. J Neurosurg 94:8418452001J Neurosurg 94:

5.

Clarke DBLeblanc RBertrand Get al: Meningeal melanocytoma. Report of a case and a historical comparison. J Neurosurg 88:1161211998J Neurosurg 88:

6.

Cordoba ATunon TVazquez JJ: Melanocitoma meningeo. Presentacion de un caso y revision de la literature. Arch Neurobiol 52:93991989Arch Neurobiol 52:

7.

Ferracini RGardini GBrisigotti Met al: Metastasizing meningeal melanocytoma. Tumori 66:4054081980Tumori 66:

8.

Leonardi MALumenta CBStolzle Aet al: Unusual clinical presentation of a meningeal melanocytoma with seizures: case report and review of the literature. Acta Neurochir 140:6216281998Acta Neurochir 140:

9.

Lesoin FLeys DPasquier Fet al: Melanotic meningioma. Report of a case and review of the literature. Neurochirurgia 28:2052071985Neurochirurgia 28:

10.

Limas CTio FO: Meningeal melanocytoma (“melanotic meningioma”). Its melanocytic origin as revealed by electron microscopy. Cancer 30:128612941972Cancer 30:

11.

Meyer DGe JBlinder KJet al: Malignant transformation of an optic disk melanocytoma. Am J Ophthalmol 127:7107141999Am J Ophthalmol 127:

12.

Nakagawa HHayakawa TNiiyama Ket al: Long-term survival after removal of primary intracranial malignant melanoma. Case report. Acta Neurochir 101:84881989Acta Neurochir 101:

13.

O'Brien TFMoran MMiller JHet al: Meningeal melanocytoma. An uncommon diagnostic pitfall in surgical neuropathology. Arch Pathol Lab Med 119:5425461995Arch Pathol Lab Med 119:

14.

Rades DTatagiba MBrandis Aet al: Stellenwert der Strahlentherapie bei der Behandlung des meningealen Melanozytoms. Strahlenther Onkol 178:3363422002Strahlenther Onkol 178:

15.

Ray BSFoot NC: Primary melanotic tumors of the meninges: resemblance to meningiomas. Report of two cases in which operation was performed. Arch Neurol Psychiatry 44:1041171940Arch Neurol Psychiatry 44:

16.

Rodriguez y Baena RGaetani PDanova Met al: Primary solitary intracranial melanoma: case report and review of the literature. Surg Neurol 38:26371992Surg Neurol 38:

17.

Russell DSRubinstein LJ: Pathology of Tumors of the Nervous Systemed 5. London: Arnold1989792808

18.

Sharma PMSangal KMalik Pet al: Malignant transformation of optic disc melanocytoma? A clinical dilemma at presentation with a review of the literature. Ophthalmologica 216:2922952002Ophthalmologica 216:

19.

Shields JAShields CLEagle RC Jret al: Malignant melanoma associated with melanocytoma of the optic disc. Ophthalmology 97:2252301990Ophthalmology 97:

20.

Skarli SOWolf ALKristt DAet al: Melanoma arising in a cervical spinal nerve root: report of a case with a benign course and malignant features. Neurosurgery 34:5335371994Neurosurgery 34:

21.

Theunissen PSpincemaille GPannebakker Met al: Meningeal melanoma associated with nevus of Ota: case report and review. Clin Neuropathol 12:1251291993Clin Neuropathol 12:

22.

Vasdev ADavid PVillemot Det al: Apparently primary malignant melanoma of the cerebellopontine angle. One case. J Neuroradiol 17:1521561990J Neuroradiol 17:

23.

Virchow R: Pigment und diffuse Melanose der Arachnoides. Arch Pathol Anat 16:1801821859Virchow R: Pigment und diffuse Melanose der Arachnoides. Arch Pathol Anat 16:

24.

Woodruff WW JrDjang WTMcLendon REet al: Intracerebral malignant melanoma: high-field-strength MR imaging. Radiology 165:2092131987Radiology 165:

25.

Yamane KShima TOkada Yet al: Primary pineal melanoma with long-term survival: case report. Surg Neurol 42:4334371994Surg Neurol 42:

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