Final Diagnosis -- Melanotic Schwannoma

FINAL DIAGNOSIS

Melanotic Schwannoma.

DISCUSSION

In 1932 Millar described an unusual pigmented neural tumor arising from a sympathetic nerve in the thoracic region. The term melanotic schwannoma was later coined by Fu et al. in 1974.

Melanotic schwannoma (MS) is an extremely rare soft tissue tumor that at the ultrastructural level demonstrates features of Schwann cells accompanied by melanosomes in different stages of maturation [2]. It accounts for less than 1 % of all primitive nerve sheath tumors; however, the exact incidence is not known due to the small case numbers reported so far [4, 2]. Since its first description, fewer than 200 cases and small series have been described [3]. The peak age of melanotic schwannoma is between the third and fifth decade [2, 4]. An equal sex distribution is reported [2]. There are two histological types of MS: non-psammomatous and psammomatous. While non-psammomatous tumors affect cervicothoracic spinal nerves and paraspinal ganglia, psammomatous tumors also involve visceral autonomic nerves such as those in the intestinal tract and the heart [4]. The distinction between the two entities is important because 50 % of patients with psammomatous tumors have the autosomal dominant disorder called Carney complex [2]. It has been previously reported that MS should be considered as an aggressive rather than benign tumor because of the high dissemination rate (up to 44 %) and disease-related mortality of up to 17 % [3].

Even to date, the histological diagnosis of MS is challenging due to the lack of specific markers that distinguish the entity from primary or metastatic melanoma. The BRAF V600E mutation, which was not present in the current case, is detected in over 90 % of melanomas; however, a negative result does not exclude melanoma.

In a series with 25 cases that were initially diagnosed as MS, it has been suggested that combined morphological and GNAQ mutational analyses should be used to discriminate MS from other melanocytic lesions [2]. More recently, however, genome-wide DNA methylation profiling using 450k arrays appears promising as a molecular tool for reliable stratification of CNS melanocytic tumors [1]. The authors reported that GNAQ mutations segregated with tumors histologically diagnosed as melanocytoma, a meningeal-based tumor found in the posterior fossa and upper spinal cord and not associated with nerve roots. At the molecular level, melanotic schwannoma harbored a complex karyotype with recurrent monosomy of chromosome 22q as well as chromosomal gains and losses involving chromosomes 1, 17p and 21. Nevertheless, the clinicopathological spectrum of primary melanocytic tumors of the CNS is still the subject of intense investigation.

REFERENCES

1. Koelsche C, Hovestadt V, Jones DTW, Capper D, Sturm D, Sahmet F et al (2015) Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles. Brain Pathol 25:202-208.
2. Küsters-Vanvelde HVN, van Engen-van Grunsven IACH, Küsters B, van Dijk MRCF, Groenen PJTA, Wesseling P et al (2010) Improved discrimination of melanotic schwannoma from melanocytic lesions by combined morphological and GNAQ mutational analysis. Acta Neuropathol 120:755-764.
3. Torres-Mora J, Dry S, Li X, Binder S, Amin M, Folpe AL (2014) Malignant melanotic schwannian tumor: a clinicopathologic, immunohistochemical, and gene expression profiling study of 40 cases, with a proposal for the reclassification of "melanotic schwannoma". Am J Surg Pathol 38:94-105.
4. Zhang H, Yang G, Chen H, Wei B, Ke Q, Guo H et al (2005) Clinopathological, immunohistochemical, and ultrastructural study of 13 cased of melanotc schwannoma. Chines Med J 118:1451-1461.

Contributed by Julia Velz, Marian Christoph Neidert, Olivia Lauk, Ilhan Inci, David Bellut, Elisabeth Rushing