Case Study 12 Gabrielle Yeaney, M.D.

19-year-old man with a past medical history of ALL who presents with a several week history of intermittent falls secondary to his legs giving out on him. He also describes sensory changes in his legs bilaterally. Describe the MRI findings (location, enhancement, mass effect). Question 1

MRI sagittal T1 w/o and w/contrast

MRI axial T2

MRIs show an enhancing intradural, extramedullary mass at the thoracic (T6-T7) level on the right side extending through a neural foramen causing compression of the spinal cord. Answer

Question 2 What is in the differential diagnosis of an intradural, extramedullary spinal lesion?

Answer Schwannoma Meningioma Hemangiopericytoma Solitary fibrous tumor Melanocytic neoplasm Inflammatory / infectious (sarcoidosis, TB) Vascular malformation Mesenchymal chondrosarcoma For this case specifically, you could include chloroma since the patient has a history of ALL, but it would be unusual.

Question 3 You are called for an intraoperative consultation. A squash preparation is performed. Due to the firmness of the tissue, a frozen section is also done. What is your intraoperative diagnosis? (A. Neoplastic/Defer/Non- neoplastic, B. ________) Click here to view slides.here

Answer A. Neoplastic B. Schwannoma

Question 4 Review the permanent section. What are the classic architectural features seen in this neoplasm? Click here to view slide.here

Answer This classic biphasic pattern is shown with compact (Antoni A) and loose (Antoni B) areas. Verocay bodies, foci with nuclear palisading, are present in Antoni A areas.

Question 5 Sometimes this tumor can appear histologically similar to fibrous meningioma or tanycytic ependymoma, given the cellular elongation and spindled patterns in all. What immunohistochemical stains would you use to differentiate the neoplasms? Give a panel of at least 3 markers and state whether positive or negative.

Answer An immuno-panel including S100, epithelial membrane antigen (EMA) and glial fibrillary acidic protein (GFAP) would be useful. The following staining patterns are expected: meningioma (S100 -, EMA +, GFAP -); ependymoma (S100 +, EMA may have focal dot-like cytoplasmic reactivity, GFAP ++ especially in pseudorosettes); schwannoma (S100 ++, EMA -, GFAP may have patchy reactivity). Schwannomas have more reticulin fibers (not an immunostain) and stronger expression of collagen IV and laminin than tanycytic ependymomas.

Question 6 What is "ancient change"?

Answer Ancient change is nuclear pleomorphism and hyperchromasia and is frequently seen in schwannomas. This "atypia" represents a degenerative phenomenon rather than a true neoplastic atypia/anaplasia, as it is not associated with cell proliferation. Schwannomas can have vascular hyalinization, stromal myxoid change and cystic change.

Question 7 What hereditary disease is associated with finding multiple tumors like this?

Answer Neurofibromatosis 2 (central neurofibromatosis) is an autosomal dominant disorder associated with schwannomas. The NF2 gene is found on chromosome 22q12, and its gene product is merlin, or schwannoma. Bilateral vestibular schwannomas and/or meningiomas, multiple cutaneous/craniospinal schwannomas, glioma, lens opacity (cataract) are associated.

Question 8 True or False. In general, malignant peripheral nerve sheath tumors arise from this neoplasm.

Answer False. MPNST is a malignant tumor arising from or differentiating towards cells intrinsic to peripheral nerves, but it should nto be viewed as a malignant counterpart to schwannoma. True malignant schwannomas are exceedingly rare. MPNSTs are often seen in association with NF1 (von Recklinghausen disease), and half of MPNSTs are derived from neurofibromas.

Question 9 What is the prognosis and standard treatment for this neoplasm?

Answer Most classic schwannomas are cured surgically.