Immunohistochemistry and Molecular Testing:

The following additional immunostains resulted positive: desmin x 2 (focal), myogenin (focal), S-100 (focal), TLE-1 (weak), and MyoD1 (focal).

The following additional immunostains resulted negative: H3K27me3, EMA, SOX-10, STAT-6, MUC-4, CD34, SMA, and cytokeratin AE1/AE3.

Additional testing includes: No SS18/SYT rearrangement is detected by FISH

Microscopic description:

Fascicles and broad whorls of relatively uniform, spindle cells with alternating cellular and hypocellular areas (tapestry or marbled pattern). Stroma is vascularized and varies from myxoid to collagenous. Mitoses are often numerous and coagulative necrosis is common.

Heterologous mesenchymal differentiation occurs in 10-15% of cases and include:
  • Rhabdomyoblastic (malignant triton tumor)
  • Osteosarcomatous, chondrosarcomatous
  • Rarely angiosarcomatous, liposarcomatous

The loss of H3K27me3 stain, and focal presence of desmin, myogenin, and Myod1 staining support a diagnosis of Malignant Peripheral Nerve Sheath Tumor With Rhabdomyomatous Differentiation (Malignant Triton Tumor).

Discussion:

Malignant peripheral nerve sheath tumors are uncommon accounting for 5%-10% of soft tissue sarcomas. The term Malignant Triton Tumor may be used for an MPSNT with rhabdomyoblastic differentiation and accounts for about 5% of all MPNSTs. The term “triton” was derived from the newt salamanders, also known as “Tritones,” used as a model organisms in neoplastic neuromuscular experiments.

Fifty percent of malignant Triton tumors are associated with Neurofibromatosis Type 1 (NF1), and 40% of cases are sporadic arising from a peripheral nerve or preexisting benign nerve sheath tumor.

The tumor presents as a painful or painless firm enlarging mass in a variety of locations including the head and neck, extremities, trunk, buttock, retroperitoneum, and mediastinum. Intracranial locations have also been identified.

About 80% of all high-grade MPNSTs exhibit complete loss of PRC2 activity through loss of the PRC2 core component (EED or SUZ12) and complete loss of H3K27me3 expression. Immunohistochemically, MPNST may be positive for S100 (< 50% of tumours), SOX10 (< 70%), and GFAP (20–30%). The loss of H3K27me3 expression has become a useful diagnostic tool in high-grade MPNST. 

Malignant Triton Tumors have a poor prognosis with a 5-year survival rate of 5-15% in contrast to 50-60% for MPNST.

References:

Brooks JSJ. Disorders of soft tissue. In: Sternberg SS, editor. Diagnostic surgical pathology. 3. Philadelphia: Lipincott Williams and Wilkins; 1999. pp. 131–221.

Kang Y, Pekmezci M, Folpe AL, Ersen A, Horvai AE. Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma. Mod Pathol. 2014 Jan;27(1):55-61. doi: 10.1038/modpathol.2013.115. Epub 2013 Aug 9. PMID: 23929265.

Prieto-Granada CN, Wiesner T, Messina JL, Jungbluth AA, Chi P, Antonescu CR. Loss of H3K27me3 Expression Is a Highly Sensitive Marker for Sporadic and Radiation-induced MPNST. Am J Surg Pathol. 2016 Apr;40(4):479-89. doi: 10.1097/PAS.0000000000000564. PMID: 26645727; PMCID: PMC4882106.

Li G, Liu C, Liu Y, et al. Analysis of clinical features and prognosis of malignant triton tumor: A report of two cases and literature review. Oncol Lett. 2015;10(6):3551-3556. doi:10.3892/ol.2015.3762

Weiss SW, Goldblum JR. Malignant tumors of peripheral nerves. In: Weiss SW, Goldblum JR, editors. Enzinger and weiss’s soft tissue tumors. 5. China: Mosby Elsevier; 2008. pp. 903–944.

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