CPC # 69: MRI & MELANIN & Dx PRIMARY MELANOCYTOMA

Today you get to see see what melanin looks like on MRIs of some of my patients.  

Melanocytes are normal, neural crest-derived cells present in the human leptomeninges (pia and arachnoid membranes) primarily at the base of the brain, the posterior fossa, and around the upper cervical spinal cord.  They are very close to cells with POMC expressed to some degree.

Meningeal melanocytomas are rare benign primary melanocytic tumors of the CNS that are derived from leptomeningeal melanocytes. They can occur anywhere along the neuraxis but are most commonly found in the spinal canal near the foramen magnum, as well as the posterior cranial fossa, Meckel cave, or adjacent to cranial nerve nuclei based on embryological movements.

Key point:  When these tumors are found in the trigeminal cave, then they are associated with a nevus of the dermatomes corresponding to the trigeminal nerve on the face. The benign dermal melanocytic nevus usually involves the ophthalmic (Va) and maxillary (Vb) divisions of the trigeminal nerve (CN V).  This again shows the neural create connections and the neuroplasticity pathways one should expect in melanogenesis from these movements in mammals.

Primary melanocytic tumors of the CNS can manifest as solid masses or as diffuse dissemination within the subarachnoid space. They range in histologic grade from benign to malignant, differentiating between the following entities:

• meningeal melanocytoma: benign mass-forming proliferation
• meningeal melanoma: malignant mass-forming proliferation
• meningeal melanocytosis: diffuse meningeal benign melanocytic proliferation
• meningeal melanomatosis: diffuse meningeal malignant melanocytic proliferation

Melanocytomas are more common in women (mean age 45-50 years old). A prolonged evolution of clinical signs of myelopathy or radiculopathy prior to surgical resection (from 5 to 10 years) has been documented.

I believe this is true because women tend to wear more clothing over their bodies due to cultural and societal reasons.

Approximately 100 cases of melanocytomas have been reported in the CNS (brain and spinal cord) since Limas and Tio coined the term "meningeal melanocytoma" in 1972. In the spinal cord, most cases of melanocytomas are found in the extramedullary intradural compartment, at the cervical and thoracic spinal levels. An intramedullary location as our case depicts is extremely rare, with only 24 cases reported before.

The unique paramagnetic properties of melanin result in a relatively specific MRI pattern for melanocytoma, consisting of iso- or hyperintensity on T1WI and iso- or hypointensity on T2WI, and with homogeneous enhancement.  The differences in MRI signal intensities relate to a variable degree of tumor melanization.

Paramagnetic means it is drawn to magnetic fields.  This is a clue why the tumor was in this location.

Definitive diagnosis is based solely on histopathological and immunohistochemical examination.

The distinction between melanocytoma and melanoma rests on the identification of cytologic atypia, mitotic activity, necrosis, and neural parenchymal invasion.

MIB-1 (Ki-67) labeling index seen in melanocytomas is low (0%-2%) while in primary melanomas is higher (2%-15%). Based on a proposition by Brat et al. the WHO classification assigns an intermediate grade to melanocytomas with increased mitotic activity and infiltrative growth that fail to meet all characteristics of malignant melanoma. In this case, MIB-1 (Ki-67) proliferation index was 5% and a definitive diagnosis of intramedullary Intermediate-grade melanocytoma of the thoracic spine was made.

CURRENT CENTRALIZED MEDICINE BELIEFS

Although classified as benign, meningeal melanocytomas may behave aggressively and a limited number may transform into malignant melanomas. Complete excision is the treatment of choice, however, this is often not possible as intra-operative hemorrhage may be severe. Furthermore, local recurrence has been reported even after gross total removal. Due to the risk of tumor recurrence even after complete excision, adjuvant radiation therapy is advised in cases of both complete and incomplete resection.  I no longer believe this.

EPIDEMIOLOGY

Peak presentation is in the fourth and fifth decades, although these tumors have been diagnosed in all age groups. Occurrence in children is very rare!

RADIOLOGY IMAGING

The patient presented after breast cancer resection with a 2-year history of progressive paraparesis, paresthesia, and dysesthesia in the left lower limb. Neurological examination demonstrated generalized hyperreflexia and clonus of the left foot.

The above MRI is done on a 1.5 Tesla magnetic and shows a solitary well-defined fusiform intramedullary lesion involving the spinal cord at the T8-T11 level, hypointense on T2WI, moderate hyperintense on T1WI, and presenting homogeneous enhancement of its solid component after gadolinium administration.

Lesion associates a cystic component in its cranial pole, and presents susceptibility artifacts in the T2WI-GRE corresponding to its melanin component and the presence of degraded blood products.

T2WI hyperintense per focal tumoral edema at the T5-T7 levels and conus medullaris is noted, suggestive of myelopathy.

OTHER IMAGES:

3 case questions are available

Q: The presence of hyperintensity on T1WI can be an important clue leading to a specific diagnosis, as happens in this case above. Which are the causes of T1 hyperintensity?

A: Melanin. Gadolinium. Fat. Blood forming proteinaceous substance. Some paramagnetic stages of blood. Mineralization. Slowly-flowing blood. Calcium. (Pic below)

Q: What's the most frequent T1WI appearance of meningeal melanocytomas?

A: Isointense or hyperintense depending on the amount of melanin content present.

Q: What's the most frequent T2WI appearance of meningeal melanocytomas?

A: Isointense or hypointense depending on the amount of melanin content present.

The slide below reminds us that when we are looking for melanin loss we should see it missing in T1 weighted MRI images.

Radiological differential diagnosis includes:

• primary or metastatic malignant melanoma
• melanotic schwannoma
• melanotic meningioma
• melanoblastosis
• cavernous malformation
• astrocytoma
• ependymoma

Operation report:

Tumor resection was performed through osteoplastic laminectomy and under electrophysiologic intraoperative monitoring.  Tumor fragments were soft, brownish, and hemorrhagic.  Melanin tumors are always bloody because they are always associated with brisk blood flow due to their need for massive oxygen consumption.  This mimics what we see in retinal bleeds around the RPE and Bruch's membrane.

PATHOLOGY SLIDES

H&E stained slides above show in sequence sheets and nests of cells with mild nuclear pleomorphism and prominent nucleoli; note the marked melanin pigment deposition. An immunohistochemistry study revealed positivity for melanocytic markers Melan A and HMB45. MIB-1 (Ki-67) proliferative mitotic index of 5%.

KEY BLOG POINT: This index clued me in that her previous breast cancer was likely related to this mass and its location.  She had a WiFi router under her bed in her apartment at the level of her mid-thoracic spine.

Meningeal melanocytomas are most commonly found in the cervical and thoracic regions (intrathecal-extramedullary). Within the spine, melanocytomas present as intradural masses, and maybe intradural extramedullary or rarely intramedullary. They are most commonly found in the upper cervical region, as melanocytes are most concentrated at this location. I believe the real reason is that this area is usually covered and not illuminated by sunlight.  Even more interesting is they are less common in the intracranial compartment because rarely do we lose all VUV-IR-A inside the brain.  We would most commonly see this in glioblastoma multiformans cases instead.

CITES

• 1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumors of the central nervous system. (2007) Acta neuropathologica. 114 (2): 97-109. doi:10.1007/s00401-007-0243-4 - Pubmed
• 2. Karikari IO, Powers CJ, Bagley CA, Cummings TJ, Radhakrishnan S, Friedman AH. Primary intramedullary melanocytoma of the spinal cord: a case report. (2009) Neurosurgery. 64 (4): E777-8; discussion E778. doi:10.1227/01.NEU.0000341516.22126.AA - Pubmed
• 3. Liubinas SV, Maartens N, Drummond KJ. Primary melanocytic neoplasms of the central nervous system. (2010) Journal of clinical neuroscience: official journal of the Neurosurgical Society of Australasia. 17 (10): 1227-32. doi:10.1016/j.jocn.2010.01.017 - Pubmed
• 4. Czarnecki EJ, Silbergleit R, Gutierrez JA. MR of spinal meningeal melanocytoma. (1997) AJNR. American journal of neuroradiology. 18 (1): 180-2. Pubmed
• 5. G.Q. Hou, J.C. Sun, X.J. Zhang, B.X. Shen, X.J. Zhu, L. Liang, X.L. Zhang. MR Imaging Findings of the Intraspinal Meningeal Melanocytoma: Correlation with Histopathologic Findings. (2012) American Journal of Neuroradiology. 33 (8): 1525. doi:10.3174/ajnr.A2987 - Pubmed
• 6. Wagner F, Berezowska S, Wiest R, Gralla J, Beck J, Verma RK, Huber A. Primary intramedullary melanocytoma in the cervical spinal cord: Case report and literature review. (2015) Radiology case reports. 10 (1): 1010. doi:10.2484/rcr.v10i1.1010 - Pubmed
• 7. Brat DJ, Giannini C, Scheithauer BW, Burger PC. Primary melanocytic neoplasms of the central nervous systems. (1999) The American journal of surgical pathology. 23 (7): 745-54. Pubmed