Coexistent intracerebral metastatic melanoma and meningioma
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.198212
Source of Support: None, Conflict of Interest: None
Coexistence of multifocal neural crest tumors, namely meningioma, melanoma, and nerve sheath tumors, is termed as neurocristopathy. Neurofibromatosis is the commonest form of neurocristopathy. We report a rare case of frontal lobe metastatic melanoma coexistent with a parietal lobe meningioma, in the absence of any stigmata of neurofibromatosis.
Keywords: Coexistent, intracerebral, melanoma, meningioma, metastatic, neurocristopathy,
Melanomas and meningiomas are tumors of neural crest origin. Their coexistence is termed as neurocristopathy. We report a case of parietal lobe meningioma existing with a metastatic melanoma in the frontal lobe. Multifocal neural crest tumors necessitate a thorough radiological examination for investigating the presence of a neurocristopathy.
A 50-year-old woman complained of headache and slurred speech since the past 1 month. She had chronic hypertension and was on anti-hypertensive therapy.
Her magnetic resonance imaging (MRI) showed two distinct extra-axial lesions [Figure 1]a and [Figure 1]b. The frontal lobe mass measured 3.3 × 3.3 × 3.8 cm, and the parietal lobe mass measured 3.8 × 5.6 × 4.4 cm. Both masses were reported on radiology as meningiomas. No significant family history or stigmata of neurofibromatosis was found. At surgery, the frontal mass was observed to have brownish black color, and hence, sent for intraoperative diagnosis. The frozen section showed atypical cells with cytoplasmic brownish granules suggestive of a melanocytic lesion.
Subsequently, the frontal mass was resected in toto without any vascular damage [Figure 2]a. Histopathology showed a highly cellular tumor. Cells showed abundant brownish pigment, nuclear pleomorphism, brisk mitoses, and tumor necrosis [Figure 3]a, [Figure 3]b and [Figure 4]a. Thus, a diagnosis of malignant melanoma was made. Immunohistochemistry (IHC) revealed that the tumor cells were positive for melanocytic markers S-100 and human melanoma black (HMB 45) [Figure 4]a inset] but negative for epithelial membrane antigen (EMA), which is a marker for meningothelial cells and carcinoma. Proliferative index by methylation-inhibited binding protein 1 (MIB-1) was 40%–50%.
The parietal mass was firm and grey-white. It was resected en bloc. Histopathology showed the typical features of a meningioma. On immunohistochemistry (IHC), tumor cells were positive for epithelial membrane antigen (EMA) [Figure 4]b and vimentin but negative for melanocytic markers HMB-45, thus confirming the diagnosis of meningioma.
Within 2 weeks after surgery, the patient complained of loose motions and abdominal distention. Ultrasonography showed multiple, isoechoic hepatic nodules suggestive of metastases. Chest radiographs showed similar metastatic nodules within the left lung. Hepatic nodule biopsy was attempted; however, the tissue was inadequate to give a definite opinion. A repeat biopsy was not possible owing to the deteriorating clinical condition.
On questioning, the patient revealed that a blackish skin lesion in the neck region was biopsied in a private hospital a few months ago [Figure 2]b. The histopathology report showed a cutaneous melanoma. In view of the histopathology report, we considered the cutaneous neck lesion as the primary melanoma, with subsequent metastases to the brain, liver, and lung. The patient expired 1 month after surgery.
Primary central nervous system (CNS) melanoma forms 1% of all primary melanomas;, CNS is the third most common site of metastases from a melanoma; and, metastatic melanoma form 9% of CNS metastases. Primary CNS melanocytic lesions include neurocutaneous melanosis, melanocytoma, primary leptomeningeal melanomatosis, and malignant melanoma.
Neurocutaneous melanosis and melanomatosis present as diffuse, discolored thickening of leptomeninges. The former is a phakomatosis associated with Dandy–Walker or Sturge– Weber syndrome More Details. Melanocytoma is a benign, solitary tumor, while primary melanoma is an aggressive tumor. Neurocutaneous melanosis and melanocytoma have malignant potential.
Melanocytic lesions on MRI are usually hyperintense on T1- and hypointense on T2-weighted images, and show homogenous contrast enhancement. These findings are due to indole quinolone and semiquinolone free radicals of melanin. Amelanotic melanoma is hypointense on T1- and hyperintense on T2-weighted images. Lesions with at least 10% melanin will show typical imaging characteristics of melanotic melanoma.
Kan et al., reported two coexistent cerebral tumors that were misdiagnosed as meningioma on MRI and later diagnosed as melanoma on histopathology. The frontal lobe mass in our case was misdiagnosed as meningioma.
MRI cannot distinguish between primary and metastatic CNS melanomas. Both will be positive for melanocytic markers like S-100 and HMB-45. However, EMA positivity is absent in the former and present in the latter.,
It is important to distinguish between primary and metastatic CNS melanoma. Both can be surgically resected. If the tumor is in vital areas of the brain, it is resected subtotally. Primary CNS melanoma does not respond well to radiotherapy and chemotherapy, unlike metastatic CNS melanoma. The drugs used for chemotherapy include dacarbazine, temozolomide, and ipulimumab., Our patient had a primary cutaneous melanoma, which later metastasized to the CNS, liver, and lungs.
Other CNS tumors with melanocytic differentiation include a schwannoma, medulloblastoma, teratoma, gliosarcoma, and craniopharyngioma. All of them can be distinguished by their typical histopathology and immunohistochemistry findings.
Melanomas, meningiomas, and peripheral nerve sheath tumors are of neural crest origin. Complex neurocristopathy is a multifocal aberrant proliferation of neural crest tissues. Neurofibromatosis type 1 is its most common example, manifesting with a coexistent meningioma, glioma, schwannoma, neurofibroma, and cutaneous melanoma. Concurrent tumors of neural crest origin as reported in literature ,,, are tabulated in [Table 1].
Melanoma can also coexist with tumors of non-neural crest origin, such as renal cell carcinoma, bilateral breast carcinoma, uterine fibromatosis, and intestinal adenomatous polyposis. Our patient showed a meningioma coexistent with cutaneous melanoma along with CNS metastases, and thus can be classified under the broad category of neurocristopathy.
Rahmah et al., reported a pigmented atypical meningioma masquerading as a metastatic melanoma owing to the presence of brown pigment within it. Han et al., also reported the diagnostic difficulty in differentiating a pigmented meningioma during performance of an intraoperative diagnosis. Special stains such as Prussian blue can identify the brown hemosiderin pigment. In our patient, using Masson Fontana stain and bleach technique, the brown cytoplasmic pigment was proven to be melanin.
A melanoma and a meningioma in the brain or spinal canal can coexist in the form of a neurocristopathy, can mimic each other on MRI, can show metaplastic transformation into each other, and can also show tumor-to-tumor metastases. Identification of multiple neural crest tumors should alert the clinician toward the presence of a neurocristopathy.
All efforts to distinguish between a primary and metastatic melanoma of the CNS should be made on the basis of detailed clinical history and a full-body clinical examination. MRI with contrast study should be done preoperatively, and the diagnosis should be confirmed on histopathology. This is important because both primary and metastatic melanoma of the CNS have a different prognosis and require different treatment protocols.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]