Dense pattern of embryonal rhabdomyosarcoma, a lesion easily confused with alveolar rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group

Abstract

Objectives: To examine whether the frequency of fusion-negative alveolar rhabdomyosarcoma (ARMSn) increased coincident with changes in the definition of alveolar histology.

Methods: We re-reviewed alveolar rhabdomyosarcoma (ARMS) in the Children's Oncology Group study D9803, comparing histopathology with fusion status.

Results: Our review of 255 original ARMS cases (compared with a control group of 38 embryonal rhabdomyosarcomas [ERMS] cases) revealed that many had an ARMS-like densely cellular pattern with cytologic features and myogenin expression more typical of ERMS. Following re-review, 84 (33%) cases of original ARMS were rediagnosed as ERMS. All reclassified ERMS, including dense ERMS, were fusion negative, whereas 82% of confirmed ARMS cases were fusion positive. Total ARMS diagnoses returned to historic rates of 25% to 30% of all rhabdomyosarcomas, and ARMSn decreased from 37% to 18% of ARMS cases. The outcome of reclassified ERMS was similar to confirmed ERMS.

Conclusions: To address the role of fusion status in risk stratification, pathologists should include both a histologic diagnosis and an evaluation of fusion status for all new ARMS diagnoses.

Keywords: Alveolar rhabdomyosarcoma; Embryonal rhabdomyosarcoma; Histologic classification; Myogenin; Rhabdomyosarcoma.

Figure 1

Distribution of histologic patterns in reclassified embryonal rhabdomyosarcoma. Combined histology indicates tumors with codominant patterns, including sclerosing/dense or sclerosing/spindled patterns.

Figure 2

Event-free survival (P < .001) (A) and overall survival (P = .018) (B) of stage 2/3, group III reclassified embryonal rhabdomyosarcoma (rcERMS) cases vs original and confirmed alveolar rhabdomyosarcoma (ARMS) and ERMS cases enrolled in the D9803 study.

Image 1

Rhabdomyosarcoma histologies (see Appendix 1 for a description). A, Alveolar rhabdomyosarcoma, classic pattern. B, Alveolar rhabdomyosarcoma, solid pattern. C, Embryonal rhabdomyosarcoma, typical pattern. D, Embryonal rhabdomyosarcoma, dense pattern. E, Embryonal rhabdomyosarcoma, botryoid pattern. F, Embryonal rhabdomyosarcoma, spindle cell pattern. G, Rhabdomyosarcoma, sclerosing pattern. H, Embryonal rhabdomyosarcoma, epithelioid pattern. I, Mixed rhabdomyosarcoma.

Image 1

Rhabdomyosarcoma histologies (see Appendix 1 for a description). A, Alveolar rhabdomyosarcoma, classic pattern. B, Alveolar rhabdomyosarcoma, solid pattern. C, Embryonal rhabdomyosarcoma, typical pattern. D, Embryonal rhabdomyosarcoma, dense pattern. E, Embryonal rhabdomyosarcoma, botryoid pattern. F, Embryonal rhabdomyosarcoma, spindle cell pattern. G, Rhabdomyosarcoma, sclerosing pattern. H, Embryonal rhabdomyosarcoma, epithelioid pattern. I, Mixed rhabdomyosarcoma.

Image 2

A, The solid pattern of alveolar rhabdomyosarcoma (ARMS) shows monomorphic round cell cytology with vesicular chromatin and inconspicuous nucleoli (H&E, ×400). B, Myogenin expression is strong and diffuse in solid-variant ARMS (×200). C, The dense pattern of embryonal rhabdomyosarcoma (ERMS) shows uniformly dense cellularity superficially resembling solid ARMS; however, the angulated nuclei and variably prominent nucleoli allow diagnosis of ERMS (H&E, ×400). D, Dense ERMS shows moderate myogenin expression (×400).