CNS & pituitary tumors

• CNS WHO grade 2 glial neoplasm with a variably papillary architecture characterized by a radial arrangement of spindled or epithelioid to cuboidal cells around blood vessels with perivascular myxoid change (intermediate layer of Alcian blue positive myxoid stroma) and mucin rich microcyst formation (Neuro Oncol 2021;23:1231)

• Glioma with papillary architecture and perivascular myxoid change or at least focal myxoid microcysts
• Immunoreactive for glial fibrillary acidic protein (GFAP)
• For unresolved tumors, DNA methylation profile is aligned with myxopapillary ependymoma

• ICD-O: 9394/1 - myxopapillary ependymoma
• ICD-11: 2A00.0Y & XH15U1 - other specified gliomas of brain & myxopapillary ependymoma

• Incidence rates are 0.6 - 1.0 cases per 1 million person years
• M:F = 1.4 - 2.1:1
• Seen in all ages but most common in adults
• 2 age peaks: 25 - 29 years and 45 - 49 years (J Neurooncol 2016;129:251, Neuro Oncol 2015;17:588)

• Almost exclusively occurs in the conus medullaris and filum terminale of the spinal cord (Mod Pathol 1997;10:304, Minerva Chir 1997;52:629)
• Occasional examples in lateral and fourth ventricles, inside or outside the brain or in cervicothoracic spinal cord but most often is in a sacrococcygeal or presacral location; rarely reported in mediastinum, lung, uterine adnexae, etc. (Brain Tumor Pathol 2012;29:25, Clin Neuropathol 2004;23:53, Cancer 1985;56:883, J Neurooncol 1993;15:251, J Clin Neurosci 2018;47:202)
• When this tumor occurs at higher levels of neuroaxis, origin from conus / filum terminale should be excluded (Pathology 1996;28:373)

• Pathophysiology is unknown; various recurring chromosomal copy number abnormalities have been described
• No consistent structural variants or other driving mutations have been demonstrated (J Clin Neurosci 2018;50:144, Neuro Oncol 2018;20:1616)

• Well circumscribed, sharply demarcated, ovoid, contrast enhancing mass in the cauda equina / conus / filum terminale region
• Hyperintense on T1 and T2 weighted MRI with intense contrast enhancement

Contributed by Ahmed Ijaz Gilani, M.B.B.S., M.D., Ph.D.

• 6 year old girl with 1 week history of progressive upper and lower extremity weakness and bilateral upper extremity dysesthesia (Childs Nerv Syst 2022;38:223)
• 9 year old girl with slow growing painless mass in the sacrococcygeal region (Am J Dermatopathol 2021;43:e273)
• 22 year old man with acute exacerbation of chronic back pain shooting down both thighs secondary to preoperative intracranial dissemination of spinal myxopapillary ependymoma (World Neurosurg 2021;145:13)
• 32 year old man with primary seeding of myxopapillary ependymoma into multiple lumbosacral areas (World Neurosurg 2017;99:812.e21)
• 34 year old man with multifocal lumbosacral mass presenting with drop metastasis (Spinal Cord Ser Cases 2022;8:43)
• 36 year old woman with spinal cord myxopapillary ependymoma who refused surgery and presented 5 years later with paraparesis (World Neurosurg 2019;121:239)

• Surgical excision is the mainstay of treatment
• Often lifted cleanly from the operative bed; others dissected piecemeal but still in toto
  • Low risk of recurrence in either of the above scenarios
• Radiotherapy reserved for subtotally resected tumors
• Some authors recommend radiotherapy for tumors excised completely but piecemeal (Mod Pathol 1997;10:304, Neurosurgery 1992;30:202, Cancer 1985;56:883)

• Often encapsulated, soft in consistency, pink to tan-gray
• May be grossly gelatinous or show hemorrhage and cystic changes

Contributed by Moneil Patel, M.D. (Case #111)

• Intraoperative squash / smear preparation and frozen section reveals epithelioid to spindled tumor cells arranged around microcysts and forming papillary structures with perivascular myxoid change; these features are diagnostic in the appropriate clinical setting

• Most common pattern is radial arrangement of cuboidal to epithelioid elongated glial tumor cells around hyalinized fibrovascular (central, often hyalinized blood vessels) cores in a papillary configuration
• Accumulation of basophilic myxoid material around blood vessels (myxoid stroma) and in microcysts
• Myxoid material is highlighted by PAS and Alcian blue positive staining
• In cases composed of confluent sheets of epithelioid cells with little or no papillary structures, PAS and Alcian blue positivity is useful in reaching a correct diagnosis
• Fascicular growth and spindle cells are common
• Pleomorphic tumor giant cells can be seen
• Occasionally tumor cells show distinctive eosinophilic balloons; these are PAS positive spherules that demonstrate spiculated reticulin staining (Am J Surg Pathol 1996;20:1091)
• Uncommon examples reported as anaplastic myxopapillary ependymomas show hypercellularity and reduced mucin in association with at least 2 of the following features: ≥ 5 mitoses / 10 high power field, Ki67 labeling index ≥ 10%, microvascular proliferation, spontaneous necrosis (Brain Pathol 2019;29:75)

Contributed by Ahmed Ijaz Gilani, M.B.B.S., M.D., Ph.D. and Aisha Hassan Memon, M.B.B.S.

Contributed by Ahmed Ijaz Gilani, M.B.B.S., M.D., Ph.D. and Brittany Pakalniskis, M.D. (Case #399)

• Positive for GFAP (diffuse expression of GFAP distinguishes myxopapillary ependymomas from other tumors in the differential diagnosis, such as metastatic carcinomas, chordomas, paragangliomas, myxoid chondrosarcomas, schwannomas, etc.)
• Positivity for S100 is typical; CD99, vimentin and CD56 positivity is seen frequently
• Positivity for cyclooxygenase 2 (COX2) is seen in the majority of cases (60%) (Neuropathology 2006;26:422)
• Often positive for keratin AE1 / AE3 cocktail (Appl Immunohistochem Mol Morphol 2013;21:485, Appl Immunohistochem Mol Morphol 2000;8:25)

• Lower spinal mass, resection specimen:
  • Myxopapillary ependymoma, CNS WHO grade 2

• Schwannoma:
  • Arises from nerve roots (myxopapillary ependymomas usually arise in the filum terminale)
  • Usually, distinctive histological appearance from ependymoma; however, a paucicellular ependymoma with fascicular architecture may simulate schwannoma
  • No Antoni A or B areas are present in ependymomas
  • There are no nuclear or cytoplasmic inclusions in ependymomas
  • Myxopapillary ependymomas have a delicate rather than densely collagenized capsule seen in schwannomas
  • Schwannomas show pericellular reticulin and extensive immunostaining for laminin and type IV collagen
  • Both tumors are S100 and GFAP positive
  • Schwannomas show more intense staining for S100 compared with GFAP; the reverse is true for myxopapillary ependymomas
• Paraganglioma:
  • More often arises from nerve roots than ependymomas
  • Presence of zellballen pattern or ganglion cells confirms the diagnosis of paraganglioma
  • Chromogranin positive (myxopapillary ependymomas are negative)
• Chordoma:
  • Mostly extradural
  • Mucinous matrix of myxopapillary ependymoma may simulate chordoma; however, mucin distribution in chordoma is diffuse and tends not to be confined in perivascular spaces
  • Chordomas are strongly immunoreactive for low molecular weight keratins and EMA; negative for GFAP
• Metastatic adenocarcinoma:
  • Glandular differentiation, goblet or signet cells with intracytoplasmic mucin supports the diagnosis of metastatic adenocarcinoma
  • Metastatic carcinomas are keratin positive and GFAP negative
• Myxoid chondrosarcoma:
  • Myxoid or chondroid matrix with lacunar-like spaces supports the diagnosis of myxoid chondrosarcoma
  • Myxoid chondrosarcoma cells would be negative for GFAP

• WHO Classification of Tumors Editorial Board: Central Nervous System Tumours, 5th Edition, 2022, Kleihues: Histological Typing of Tumours of the Central Nervous System, 2nd Edition, 1993, Perry: Practical Surgical Neuropathology - A Diagnostic Approach, 2nd Edition, 2017

A 22 year old man was diagnosed with a myxopapillary ependymoma in the filum terminale of the spinal cord. The diagnosis was confirmed by histological examination and immunohistochemical staining. What is the most important IHC stain expressed by this tumor that distinguishes it from the other lesions included in the differential diagnosis?

1. CD99
2. GFAP
3. Keratin
4. Olig2
5. S100

B. GFAP. Diffuse immunoreactivity for GFAP distinguishes myxopapillary ependymoma from metastatic carcinoma, paraganglioma, schwannoma, chordoma and myxoid chondrosarcoma (Appl Immunohistochem Mol Morphol 2013;21:485).

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Reference: Myxopapillary ependymoma

In the 5th edition of the 2021 WHO classification for CNS, which histological grade does myxopapillary ependymoma correspond to?

1. Grade 1
2. Grade 2
3. Grade 3
4. Grade 4
5. Unassigned

B. Grade 2. The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy update 6 recommends that spinal myxopapillary ependymomas be diagnosed based on histological criteria but notes that these tumors have a clinical outcome similar to classic ependymoma and should be assigned WHO grade 2 rather than grade 1 assigned in 2016 WHO CNS (Brain Pathol 2020;30:844).

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Reference: Myxopapillary ependymoma