February 2024 Case of the Month Answer

Discussion:

The spindle to epithelioid morphology, "tapestry"-like appearance at low power (with alternating areas of hyper- and hypo-cellularity), as well as areas with frank pleomorphism/anaplasia, is a classic look for MPNST. However, these findings, additionally with scattered areas revealing rhabdomyoblastic appearance (see fourth H&E image), raise a very broad differential, including leiomyosarcoma, synovial sarcoma, cellular schwannoma, atypical neurofibroma, melanoma, de-differentiated liposarcoma, and spindle cell rhabdomyosarcoma, requiring a broad immunohistochemical workup. While the rhabdomyoblastic features, in addition to the patchy positivity for desmin, myogenin, and MyoD1 would be supportive of a rhabdomyosarcoma, the striking loss of H3K27me3 is most consistent (essentially diagnostic of) with MPNST, with rhabdomyoblastic differentiation, an entity often referred to as malignant "triton" tumor, historically named after Triturus, a genus of newts formerly known as "Triton", with remarkable limb regenerative capabilities (involving re-growth of muscle).
 
Malignant Triton Tumor (MTT) is exceedingly rare (less than ~100 cases reported) and, like other forms of MPNST, often arises in the setting of neurofibromatosis type 1 (NF1), and bares a poor prognosis (<10% 5-year survival) despite aggressive surgical resection and attempts at applying radiation and chemotherapy.
 
This case serves as an excellent example of the potential for heterologous differentiation in MPNST, which can include angiosarcomatous, osteoid, and chondroid manifestations, in addition to rhabdomyoblastic, and the utility of H3K27me3 immunostaining for imperative rule-out/rule-in of MPNST, even in the absence of a history of NF1. Like the majority of MPNSTs (regardless of whether there is a history of NF1), subsequent panel-based massively parallel sequencing analysis identified mutations in NF1 as well as TP53.

Sources:

Shetty PK, Baliga SV, Balaiah K. Malignant triton tumor: a rare case. Indian J Surg. 2013;75(Suppl 1):362-365. doi:10.1007/s12262-012-0710-6
 
Sobczuk P, Teterycz P, Czarnecka AM, et al. Systemic Treatment for Advanced and Metastatic Malignant Peripheral Nerve Sheath Tumors-A Sarcoma Reference Center Experience. J Clin Med. 2020;9(10):3157. Published 2020 Sep 29. doi:10.3390/jcm9103157
 
Pemov A, Li H, Presley W, Wallace MR, Miller DT. Genetics of human malignant peripheral nerve sheath tumors. Neurooncol Adv. 2019;2(Suppl 1):i50-i61. Published 2019 Nov 28. doi:10.1093/noajnl/vdz049