Spindle Cell / Sclerosing Rhabdomyosarcoma

See section Embryonal rhabdomyosarcoma.

The genetic abnormalities identified in spindle cell / sclerosing rhabdomyosarcoma can be categorized into three groups. The first group, congenital/infantile spindle cell rhabdomyosarcoma, shows gene fusions involving the VGLL2, SRF, TEAD1, NCOA2, and CITED2 genes. The gene fusions include SRF-NCOA2, TEAD1-NCOA2, VGLL2/NCOA2, and VGLL2-CITED2. The second group, which comprises most spindle cell / sclerosing rhabdomyosarcomas in adolescents and young adults, as well as a subset of tumors in older adults, shows the presence of MYOD1 p.Leu122Arg gene mutation. The mutation, which occurs in the DNA-binding domain of MYOD1, leads to blocking of the wildtype MYOD1 function and imparts a MYC-binding capability. The third group of spindle cell / sclerosing rhabdomyosarcoma shows no recurrent identifiable genetic alterations. The recently described intraosseous spindle cell rhabdomyosarcoma shows two gene fusions, one involving either the EWSR1 or the FUS gene being fused to the TFCP2 gene. The other is the MEIS1-NCOA2 gene fusion.

Spindle cell / sclerosing rhabdomyosarcomas present as variably circumscribed tumors, with sizes ranging from 1.5 to 35 cm. They show a white to tan cut surface with a whorled appearance. Necrosis and cystic degeneration may be present.

Spindle cell / sclerosing rhabdomyosarcoma shows variable morphology. Spindle cell rhabdomyosarcoma is characterized by cellular fascicles of spindle cells with an intersecting or herringbone growth pattern, resembling leiomyosarcoma or fibrosarcoma. The spindled neoplastic cells have pale eosinophilic cytoplasm and blunted, ovoid or fusiform, centrally located nuclei with small inconspicuous nucleoli. Mitotic figures, nuclear atypia, and hyperchromatic nuclei are often present. Primitive undifferentiated areas with round cells and hyperchromatic nuclei may also be present focally. Tadpole or strap cells, rhabdomyoblasts with elongated eosinophilic tails with cross-striations, can be observed in some cases. Sclerosing rhabdomyosarcomas show prominent hyalinization/sclerosis, with tumor cells arranged in cords, nests, microalveoli, or trabeculae in a pseudovascular growth pattern. Prominent intervening sclerosis is noted. Sclerosing areas may mimic osteosarcoma due to the extensive matrix formation. The recently described intraosseous spindle cell rhabdomyosarcomas show, apart from the typical spindle cell morphology, areas of distinctly epithelioid cells arranged in sheets and fascicles.

Immunohistochemically, spindle cell / sclerosing rhabdomyosarcoma is characterized by diffuse expression of desmin in all cases, with only focal expression of myogenin (MYF4) in most cases. MYOD1 staining can be focal or diffuse in the spindle cell tumors, but it is usually present in a diffuse pattern in the sclerosing cases. Staining for SMA and MSA is usually not present. A subset of the recently described intraosseous spindle cell rhabdomyosarcoma can also show positivity for cytokeratin and ALK.

Not clinically relevant

Congenital / infantile spindle cell / sclerosing rhabdomyosarcomas with gene fusions show a favorable clinical course. MYOD1-mutant spindle cell / sclerosing rhabdomyosarcomas follow an aggressive course despite multimodality therapy and have a poor prognosis in children and adults, with 3-year and 4-year survival rates of 36% and 18%, respectively.

VGLL2, CITED2, NCOA2, MEIS1, EWSR1, and TFCP2 gene rearrangements can be detected by FISH studies, using break-apart probes or fusion probes. Alternatively, the gene fusion can be detected by targeted RNA sequencing using next-generation sequencing platforms. MYOD1 mutations can be identified by PCR and Sanger sequencing of the hotspots or by targeted DNA sequencing on next-generation sequencing platforms.

Essential: cellular spindle cell fascicles or tumor cells in a variably sclerotic collagenous background; positivity for desmin, myogenin (focal), and MYOD1.

Desirable in selected cases: MYOD1 mutations and/or various gene rearrangements (see above).