DIAGNOSIS Malignant melanotic schwannoma
Melanotic schwannomas (MS) were first described in 1932 by Millar(8). These tumors are rare, with approximately 80 cases reported in the literature to date(14). They are of neural crest origin and are believed to arise from a common precursor for Schwann cells and melanocytes(12, 13). MS occurs about a decade earlier than other types of schwannomas with a peak in the fourth decade (range 10-92 years) with no sex predominance. Most patients present with symptoms of nerve compression(10, 12, 14). The cranial and spinal nerve roots, along with the parasympathetic chain are common locations for MS, with cases also reported in the respiratory and alimentary tracts among other sites(1, 11). Approximately 20% of patients have multiple MS and 10% of cases undergo malignant transformation(10).
Histologically, melanotic schwannomas are characterized by the typical spindle shaped neoplastic Schwann cells and melanosomes in various stages of maturation. These tumors are grossly pigmented and immunophenotypically mark for both Schwann cell markers and markers of melanocytic differentiation (9). They contain melanosomes which are typically in stages II, III (premelanosomes) and IV (mature melanosomes). MS has both non-psammomatous and psammomatous variants. The non-psammomatous variants usually involve the spinal nerves and the paraspinal ganglia (9). The psammomatous variants tend to affect nerves of the intestinal tract, heart and cranial nerves (10).
Approximately 50% of the patients with the psammomatous variant have Carney's complex, and these cases generally occurs in younger patients(2, 3). Carney's complex is an autosomal dominant, multisystem disorder characterized by myxomas (primarily involving the heart, skin and breasts), pigmented skin lesions, endocrine abnormalities, and melanotic schwannomas (3). Myxomas are the most serious finding. Endocrine abnormalities include nodular adrenal cortical hyperplasia and acromegaly due to pituitary adenomas (3, 9).
Cytologic examination of MS reveals elongated cells with long branching cytoplasmic projections, abundant melanin pigment and fusiform or rounded nuclei(7). The tumor is reactive for melanoma markers including S100, HMB45, and Melan A(14). Immunohistochemical markers S100 and HMB45 are commonly positive in MS, and GFAP and neurofilament protein are sometimes positive. Lamin and collagen type IV are positive in MS and may be useful in distinguishing MS from MM(14). As previously mentioned, 10% of MS undergo malignant transformation. Useful criteria to diagnose malignancy in a MS include the presence of necrosis, an increased mitotic rate and nuclear atypia. However, one should be careful in evaluating nuclear atypia, since benign MS can also appear rather atypical.
Distinguishing malignant melanotic schwannoma (MMS) from melanoma can be challenging. MMS typically occurs in younger patients (mean age of 33) while melanoma is more common in the fifth decade(2). The presence of nuclear palisading, high cellularity, prominent spindle cells and lack of a cutaneous primary may be helpful in rendering a diagnosis of MMS. Electron microscopy can contribute significantly to the differentiation of MMS versus melanoma. MMS cells demonstrate cell processes, have a prominent basal lamina, melanosomes and most importantly, intercellular junctions(11). Melanomas have cellular interdigitation without intercellular junctions, indented nuclei and prominent nucleoli(4). Our case demonstrated prominent intercellular junctions in addition to the external lamina, cell processes and melanosomes in all stages of maturation, supporting our diagnosis of MMS.
The importance of thorough sampling of tumors was illustrated in this case. The periphery of the lesion, where the frozen section was taken, contained only benign appearing nerve sheath components. This was confirmed by retrospective review of the frozen slides following examination of the permanent sections. With the surrounding benign peripheral nerve sheath tumor and the central malignant appearing zone, the differential diagnosis included melanotic schwannoma (benign versus malignant) and melanoma (either a sequestered primary or metastatic). Supplemental studies with immunohistochemistry were not able to adequately distinguish between MMS and melanoma. Electron microscopy was useful in rendering the diagnosis of MMS.
The reported recurrence rate for MMS ranges from 10-24%(5, 6, 12). Most paraspinal lesions do not metastasize (reported rate of metastasis of 5-26%)(5, 6, 12). Incomplete excision appears to have a negative impact on prognosis; however, radiotherapy has been shown to be beneficial even with incomplete excision. MMS involving the cranial nerves has a worse prognosis(5). 15% of patients with MMS died of their tumor(10).
Post-operatively, the patient healed well from the surgery and was neurologically intact. It was decided that close follow-up would be the best course of action. The complete resection and the small size of the lesion also weighed against radiation therapy. Follow-up imaging three months after surgery demonstrated soft tissue changes consistent with post-surgery, but no evidence of recurrence of the paraspinal mass.
Acknowledgements: Ultrastructural studies performed at the Electron Microscopy Laboratory, University of South Florida College of Medicine Tampa, Florida. The authors wish to acknowledge Dr. Santo Nicosia, Chairman, USF Department of Pathology and Cell Biology, for his consistent support and encouragement of academic endeavors.
Contributed by Elizabeth M. Sagatys, MD, Jane L. Messina, MD and Amyn M. Rojiani, MD, PhD