An 11‐Year‐Old Boy with A Sacral Spinal Mass

Clinical History and Imaging

An 11 year old boy presents with a 1‐year history of sharp sacral pain radiating to the buttock and legs, left greater than right. His past medical history is unremarkable. No focal neurologic deficits are noted on examination. However, he has a pronounced antalgic gait with a crouched, widened stance. MRI of the lumbosacral spine (Figure 1a ) respectively reveals a sagittal T1 weighted image with a slightly hypointense lesion extending from S1 to S3. The lesion is hyperintense on T2, and in the T1 weighted sagittal image the mass exhibits homogeneous contrast enhancement after Gadolinium injection. The axial imaging post contrast redemonstrates the lesion within the spinal canal. The inferior aspect is located asymmetric to the left and on lower cuts there is likely extension along an exiting nerve root due to thickening and enhancement of the left S3 nerve root (not shown). No other lesions are identified within the cervical, thoracic, or lumbar spine.

Figure 1.

 

The patient underwent S1 and S2 laminectomies for tumor resection with use of intraoperative microscope and intraoperative monitoring (SSEP, EMG, and bladder sphincter monitoring). Intraoperatively, the mass was dumbbell shaped with a small intradural and a large extradural component. The extradural portion had a well‐defined capsule. Once de‐vascularized, the extradural component was amputated from the intradural segment. It was easily separated from the bone. The calcified intradural component was easily separated from the dura. Several rootlets appeared to terminate within the mass and were sacrificed to allow for complete resection.

Gross and Microscopic Pathology

The surgical specimen consisted of 13 tan‐brown rubbery fragments of tissue ranging from 0.2 × 0.1 × 0.1cm to 1.5 × 1.5 × 1.0 cm.

The H&E stained sections reveal an epithelioid neoplasm mostly surrounded by dura but also infiltrating the adjacent soft tissue and superficially one accompanying bony fragment. The tumor cells contain moderate cytoplasm, enlarged nuclei and enlarged magenta nucleoli (Figure 1b). Atypical mitotic figures are frequently seen ranging between 4–5 per 10 high‐power field. There is no specific organization in the arrangement of the tumor cells. Although a somewhat acinar pattern is hinted, the reticulin stain is completely negative. PAS highlights the basal lamina surrounding these cells (Figure 1c).

Various antibodies employed reveal diffuse nuclear positivity with S100 antibody in the tumor cells (Figure 1d) and diffuse cytoplasmic positivity with melanoma cocktail antibody (not shown). Neurofilament, GFAP and synaptophysin identify the adjacent nerve fibers and benign ganglion cells (Figure 1e). The tumor cells are negative with desmin, myogenin, CD68, chromogranin and the cytokeratin cocktail antibodies.

Electron microscopy reveals epithelioid cells with enlarged nuclei, moderate cytoplasm that includes the usual complement of organelles such as mitochondria and rough endoplasmic reticulum (Figure 1f). In addition, many cells are noted to contain pre‐melanosomes and mature melanosomes (Figure 1g). Redundant cytoplasmic processes are present. Often the neoplastic cells are surrounded by basal lamina, and some cells reveal simple intercellular junctional complexes (Figure 1h). No other specific specialization is noted at electron microscopic levels. What is your diagnosis?

Diagnosis

Malignant peripheral nerve sheath tumor (MPNST)/ epithelioid and melanotic schwannoma.

Discussion

Primary tumors of the spinal cord are rare within the pediatric population, with 1–2.6 cases reported per one million children. 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 2.

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 1e. 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 1, as well as melanosomes in various stages of maturation (Figure 1g). These features are diagnostic of a malignant melanocytic epithelioid schwannoma, an entity encompassed within the diagnostic category of malignant peripheral nerve sheath tumor.

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 3. 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 1, 3. The presence of Luse‐bodies (interstitial bundles of long‐spaced collagen) is also suggestive of Schwannian origin 3. In the absence of electron microscopy, GNAQ mutational analysis or immunolabeling for type IV collagen and laminin may be helpful 4. 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.

In general, 10% of melanotic schwannomas are malignant. 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. 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. Post operative 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.