Malignant peripheral nerve sheath tumor (MPNST) / epithelioid and melanotic schwannoma.
Primary tumors of the spinal cord are rare within the pediatric population, with 1-2.6 cases reported per one million children (8). These tumors can be classified as extradural (30% of cases), intradural extramedullary (25%), or intramedullary (25-35%). The main differential diagnoses for extradural tumors include neuroblastoma and sarcoma, with a rare incidence of schwannomas. Intradural extramedullary tumors are most commonly schwannomas, myxopapillary ependymomas, and atypical teratoid/rhabdoid tumors. Finally, an intramedullary tumor should raise suspicion for low-grade astrocytomas, ependymomas and gangliogliomas (3).
In this case the tumor was described intraoperatively as dumbbell-shaped with a small intradural and a large extradural component, with several nerve rootlets terminating within the mass. This tumor's association with peripheral nerves is confirmed histologically and is illustrated in Figure 5. The tumor reveals an epithelioid morphology and features of malignancy, namely a high mitotic index, with atypical forms and invasion of the adjacent soft and bone tissue. Immunohistochemistry reveals positivity for S100, which is compatible with Schwannian-cell differentiation but is not specific for this cell type. The final diagnosis is achieved with the aid of electron microscopy, which reveals cell processes and pericellular basal lamina, both characteristic feature of Schwann cells (2), as well as melanosomes in various stages of maturation (Figure 7). These features are diagnostic of a malignant melanocytic epithelioid schwannoma, an entity encompassed within the diagnostic category of malignant peripheral nerve sheath tumor (7).
Melanotic schwannomas are rare tumors that do not exhibit sex predilection and present at an earlier age (mean of 38 years) compared to conventional schwannomas (5). Immunohistochemically and ultrastructurally, these tumors display both Schwannian and melanocytic features, testifying to the common origin from neural crest cells. Key ultrastructural features supportive of Schwannoma diagnosis include slender, interdigitating cell processes coated by abundant, continuous, and sometimes duplicated basal lamina, which often reveals a biphasic distribution (both pericellular and nested patterns) in tumors with melanocytic differentiation (2, 4, 5). The presence of Luse-bodies (interstitial bundles of long-spaced collagen) is also suggestive of Schwannian origin (4, 5). In the absence of electron microscopy, GNAQ mutational analysis or immunolabeling for type IV collagen and laminin may be helpful (4, 6). There are two main histological variants of melanotic schwannomas: nonpsamommatous, most often associated with spinal nerve roots, and psmamomatous, which also affect viscera, most commonly the gastrointestinal tract. Correct identification of the latter has clinical significance due to a significant association with the autosomal-dominant Carney complex (1).
In general, 10% of melanotic schwannomas are malignant (1). Histological features suggestive of malignancy include invasion, necrosis, macronucleoli, increased mitoses and abnormal mitotic figures. However, these tumors have been known to metastasize even in the absence of overt malignant histological features (9). Thus, prognosis for these patients is always reserved, and long-term follow-up is recommended.
This patient's post-operative course was uneventful. His gait is normal and his pain has completely resolved. He has no neurological deficits with no evidence of bowel/bladder dysfunction. Whole body PET scan revealed no abnormal hyper-metabolism to suggest recurrent/residual or metastatic disease. Staging CT scans revealed no evidence of metastatic disease in the chest, abdomen, or pelvis. Postoperative MRI of the lumbar spine demonstrated expected interval post-operative changes consistent with prior S1-S2 laminectomy. A small area concerning for residual/recurrent disease was noted on the 3 month follow-up MRI. Subsequently, he underwent operative exploration that confirmed no evidence of residual or recurrent tumor. He is now receiving proton beam radiation to the resection site.
The authors gratefully acknowledge the invaluable assistance of Joan Sempf, H.T. (A.S.C.P), Lisa W Keane, BS, and Linda A. Sebree in the areas of electron microscopy tissue preparation, histopathology, and immunohistochemistry, respectively.
Contributed by Celina Montemayor Garcia, MD, PhD, Carolina Sandoval Garcia, MD; Taryn Bragg, MD; Neha J Patel, MD, and Shahriar Salamat, MD, PhD.