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Journey through Metastatic Melanoma of the Central Nervous System J Nair, A Alamer, S Saif, C Torres, J Chankowsky, R del carpio

Learning Objectives To describe the conventional magnetic resonance imaging (MRI) findings of Metastatic CNS melanoma, especially the signal characteristics based on their contents. Identify different imaging patterns of CNS melanoma and their anatomic sites of involvement. Discuss the post-treatment imaging pattern.

Background Malignant melanoma represents the third most common cause for cerebral metastasis after breast and lung cancer. Central nervous system (CNS) metastasis occur in 10 to 40 % of patients with melanoma. Most of the symptoms of CNS melanoma metastasis are non-specific and depend on the location of the lesion. The majority of patients have multiple lesions, supratentorial being more common than infratentorial. Similar to other metastasis, they are predominantly located at the gray-white matter junction with surrounding significant vasogenic edema. Homogenous enhancement is seen on post contrast images.

Melanoma metastases can be divided into: 1): 1)Melanotic : Containing greater than 10% melanotic cells on histopathology. 2): Containing less than 10% melanotic cells. 2)Amelanotic : Containing less than 10% melanotic cells. However, this pattern approach is considered to be oversimplified as the amount of melanin-containing cells in metastases is extremely variable. It has been postulated that intralesional hemorrhage plays a greater role in influencing the imaging appearance of melanoma than the melanin content. Background

Our Approach An extensive search was made for melanoma of the Central nervous system at our institution, from the database available on PACS from 2005 to All cases were evaluated and based on the findings, the poster has been designed. Our MRI protocol Included: Sagittal T1W 5mm thickness. Axial T1W, T2W, FLAIR and DWI (including ADC map) 5mm thickness. Coronal T2W and GRE 5mm thickness. Post-gadolinium injection; Axial & Coronal T1W (5mm) and/or Axial T1W 3D FSPGR 1mm thickness.

Imaging Findings MRI features of Metastatic Melanoma: 1. 1.Intracranial disease:   Patterns: A.Hyper intense relative to the cortex on T1-weighted images and hypo intense relative to the cortex on T2-weighted images with post- contrast enhancement. A.Melanotic : Hyper intense relative to the cortex on T1-weighted images and hypo intense relative to the cortex on T2-weighted images with post- contrast enhancement. (Fig 1), (Fig 2)(Fig 1)(Fig 2) B.Hypo intense on T1-weighted images and iso- to hyper intense relative to the cortex on T2-weighted images with post- contrast enhancement. B.Amelanotic : Hypo intense on T1-weighted images and iso- to hyper intense relative to the cortex on T2-weighted images with post- contrast enhancement. (Fig 3), (Fig 4) (Fig 3), (Fig 4)

C.The signal intensity on T1WI and T2WI depends on the stage of hemorrhage stage; acute, early subacute, late subacute or chronic. (Fig 5) C.Hemorrhagic : The signal intensity on T1WI and T2WI depends on the stage of hemorrhage stage; acute, early subacute, late subacute or chronic. (Fig 5)(Fig 5)(Fig 5) D.Cystic : Not commonly described. The cystic portion has variable signal, usually hypo intense on T1WI and hyper intense on T2WI. (Fig 6) (Fig 6)(Fig 6) E.Subependymal : Nodular periventicular, ribbonlike signal with marked enhancement. (Fig 7) (Fig 7)(Fig 7) F.Perineural/leptomeningeal : Sugar-coating of the pial surface or along the cranial nerves. (Fig 8), (Fig 9) (Fig 8)(Fig 9)(Fig 8)(Fig 9) Imaging Findings

Fig 1 : 39-year-old male with intra-axial melanotic metastasis. The lesion is hyper intense on T1WI and hypo intense on T2WI associated with post contrast enhancement. Intra-axial Melanotic Metastasis AXIAL T1WAXIAL T2W POST-CONTRAST

Fig 2 : 78-year-old male with classic extra-axial melanotic metastasis. The lesion shows hyper intense signal on T1WI, hypo intense on T2WI with homogenous post contrast enhancement. Similar signal characteristic scalp lesion also noted. Extra-axial Melanotic Metastasis

Fig 3 : 59-year-old male with The lesion shows low signal on T1WI and high signal intensity on T2WI with homogenous post- contrast enhancement. Fig 3 : 59-year-old male with intra-axial amelanotic metastasis. The lesion shows low signal on T1WI and high signal intensity on T2WI with homogenous post- contrast enhancement. Intra-axial Amelanotic Metastasis AXIAL T1WAXIAL T2W POST-CONTRAST

Fig 4 : 47-year-old male with The lesion is of low signal on T1WI and high signal intensity on T2WI with homogenous post- contrast enhancement. Fig 4 : 47-year-old male with extra-axial amelanotic metastasis. The lesion is of low signal on T1WI and high signal intensity on T2WI with homogenous post- contrast enhancement. Extra-axial Amelanotic Metastasis AXIAL T1W AXIAL T2W POST-CONTRAST

Fig 5 : 78-year-old female with demonstrates hyper intense signal on T1WI and T2WI with blooming on GRE sequence and minimal post-contrast enhancement. Fig 5 : 78-year-old female with hemorrhagic melanoma metastasis demonstrates hyper intense signal on T1WI and T2WI with blooming on GRE sequence and minimal post-contrast enhancement. Hemorrhagic Melanoma Metastasis

Fig 6 : 78-year-old female with marginal enhancement and small hemorrhagic component. Fig 6 : 78-year-old female cystic melanoma metastasis with marginal enhancement and small hemorrhagic component. Cystic Melanoma Metastasis

Fig 7 : 39-year-old male with involvement by metastatic melanoma around the 3 rd ventricle. Fig 7 : 39-year-old male with subependymal involvement by metastatic melanoma around the 3 rd ventricle. Subependymal Melanoma Metastasis

Fig 8 : 30-year-old male with new onset cranial nerves symptoms. Post- Contrast Axial T1W images leptomeningeal involvement of the III, V, and VII/VIII nerves by metastatic melanoma. Fig 8 : 30-year-old male with new onset cranial nerves symptoms. Post- Contrast Axial T1W images show leptomeningeal involvement of the III, V, and VII/VIII nerves by metastatic melanoma. Leptomeningeal Melanoma Metastasis

Fig 9 : 30-year-old male with perimesencephalic metastasis. Fig 9 : 30-year-old male with perimesencephalic leptomeningeal melanoma metastasis. Leptomeningeal Melanoma Metastasis

2. 2.Extracranial: A. A.Spine: I.: Well defined enhancing leptomeningeal nodules of the cord and thick enhancing sheets of metastatic deposits along the conus medullaris, cauda equina and nerve roots. (Fig 10) (Fig 11) I.Spinal Cord, Cauda equina and nerve roots : Well defined enhancing leptomeningeal nodules of the cord and thick enhancing sheets of metastatic deposits along the conus medullaris, cauda equina and nerve roots. (Fig 10) (Fig 11)(Fig 10)(Fig 11)(Fig 10)(Fig 11) II.: Extensive anterior and posterior element involvement with multilevel collapse of vertebral bodies. (Fig 12) II.Vertebral bodies: Extensive anterior and posterior element involvement with multilevel collapse of vertebral bodies. (Fig 12)(Fig 12)(Fig 12) Imaging Findings

B.Involves the eye globes, extra ocular muscles, lacrimal glands and/or bony orbit. (Fig 13) B.Orbits : Involves the eye globes, extra ocular muscles, lacrimal glands and/or bony orbit. (Fig 13)(Fig 13)(Fig 13) C.Lesions show restricted diffusion signal, enhancement and possible adjacent bone erosion/infiltration. (Fig 14) C.Muscles : Lesions show restricted diffusion signal, enhancement and possible adjacent bone erosion/infiltration. (Fig 14)(Fig 14)(Fig 14) D.Involvement can be unilateral or bilateral. (Fig 15) D.Parotid glands : Involvement can be unilateral or bilateral. (Fig 15)(Fig 15)(Fig 15) E.Scattered well defined enhancing soft tissue metastatic lesion. (Fig 16) E.Scalp and neck muscles : Scattered well defined enhancing soft tissue metastatic lesion. (Fig 16)(Fig 16)(Fig 16) Imaging Findings

Spinal Metastatic Melanoma Fig 10 : Fig 10 : 45-year-old female with leptomeningeal involvement of the cervical and thoracic spinal cord, conus medullaris and cauda equina nerve roots.

Metastatic Melanoma to the Cauda Equina and nerve roots Fig 11 : Extensive metastatic disease involving the conus and cauda equina nerve roots.

Melanoma Metastasis to the Vertebral bodies Fig 12 : 47-year-old male with extensive Fig 12 : 47-year-old male with extensive vertebral metastasis.

Metastatic melanoma to the orbits. Fig 13 : 79-year-old male with metastasis to bilateral extra ocular muscles.

Metastatic melanoma to the muscles Fig 14 : 42-year-old male with metastatic melanoma to the temporalis muscle

Fig 15: 48 year old female with metastatic melanoma to Right Parotid Gland Metastatic melanoma to the Parotid gland

Fig 16: 67 year old male with metastatic melanoma to Scalp and Neck muscles Metastatic melanoma to the Scalp and Neck Muscles Metastatic melanoma to the Scalp and Neck Muscles

3. 3.Post therapeutic MR features: Treatment options:  Surgery.  Chemotherapy.  Radiation therapy.  Biological therapy.  Targeted therapy. Imaging: In addition to the reduction in size of the lesions and surrounding edema, lesions are relatively hypo intense on both T1 and T2 with peripheral hemosiderin deposition on T2WI. Minimal or no post contrast enhancement noted. (Fig. 17) Fig. 17)Fig. 17)

Fig. 17: 57-year-old female post treatment status of melanoma shows reduction in the size of the lesions and surrounding edema. Lesions are hypo intense on both T1 and T2 with peripheral blooming. Post treatment MRI features

Differential Diagnosis Anaplastic lung carcinoma. Thyroid carcinoma. Choriocarcinoma. Renal Cell carcinoma.

Conclusion Malignant melanoma has a wide spectrum of appearance with involvement of the intra and extra cranial structures. Although brain is the most common site of metastasis in the head and neck, metastatic melanoma can involve essentially any structure including the spinal cord. This pictorial review from our institution will familiarize radiologists with typical and atypical imaging features and locations of malignant melanoma on MRI when screening patients.

References Goulart CR, Mattei TA, Ramina R. Cerebral Melanoma Metastases: A Critical Review on Diagnostic Methods and Therapeutic Options. ISRN Surgery 2011;2011: Goulart CR, Mattei TA, Ramina R. Cerebral Melanoma Metastases: A Critical Review on Diagnostic Methods and Therapeutic Options. ISRN Surgery 2011;2011: Smith, AB, Rushing, EJ, and Smirniotopoulos, JG. Pigmented lesions of the central nervous system: radiologic-pathologic correlation. Radiographics. 2009; 29: 1503–1524. Escott EJ. A variety of appearances of malignant melanoma in the head: a review. RadioGraphics 2001;21(3):625–639. Isiklar I, Leeds NE, Fuller GN, Kumar AJ. Intracranial metastatic melanoma: correlation between MR imaging characteristics and melanin content. AJR Am J Roentgenol 1995;165(6):1503–1512. Isiklar I, Leeds NE, Fuller GN, Kumar AJ. Intracranial metastatic melanoma: correlation between MR imaging characteristics and melanin content. AJR Am J Roentgenol 1995;165(6):1503–1512.

Journey through Metastatic Melanoma of the Central Nervous System J Nair, A Alameer, S Saif, C Torres, J Chankowsky, R del carpio