Proximal-Type Epithelioid Sarcoma of the Head and Neck (HN): A Study with Immunohistochemical and Molecular Tests
Renee Frank, Navid Sadri, Tricia Bhatti, Jaclyn A Biegel, Virginia LiVolsi, Paul J Zhang. Hospital of the University of Pennsylvania, Philadelphia; Children's Hospital of Philadelphia, Philadelphia
Background: Proximal epithelioid sarcoma (PES) is an aggressive variant of epithelioid sarcoma most often occurring in soft tissue of proximal limbs and characterized by polygonal cells, marked nuclear atypia, and varied rhabdoid features. Morphologic and immunohistochemical (IHC) similarities between PES and malignant extra-renal rhabdoid tumors (MRT) pose a diagnostic challenge and may suggest a relationship between the two. Both tumors are extremely rare within the head and neck and both are characterized by loss of INI1/SMARCB1 expression. The molecular events involving SMARCB1 seem to differ however, with point mutations more common in MRT and deletions in PES.
Design: Three PES of HN were evaluated. The patients were ages 9, 43, and 71 years old, and tumor locations were posterior para-median neck, sinonasal, and retro-orbital respectively. Histologic and IHC sections were evaluated. Mutation analysis by direct sequencing of the promoter and 9 exons of SMARCB1, multiplex ligation-dependent probe amplification (MLPA), and whole genome single nucleotide polymorphism (SNP) array were performed on frozen tissue from the two adult cases.
Results: Morphologically the tumors were composed of poorly differentiated discohesive cells with eccentric, oval nuclei. Some tumor cells featured abundant eosinophilic inclusion-like cytoplasm, imparting a rhabdoid appearance. All tumors showed cytokeratin reactivity and lack of SMARCB1 expression; no myoid differentiation was identified by IHC. There were no mutations in the promoter region or coding sequence of the SMARCB1 gene. One of the two tumors showed heterozygous deletion in chromosome 22 by MLPA and whole genome SNP array.
Conclusions: Though rare, PES could occur in HN and should be differentiated from other HN tumors with epithelioid/epithelial differentiation by lack of SMARCB1 staining. Although positive cytokeratin and negative myoid markers favor PES over MRT, molecular analysis may further distinguish these closely related entities. The lack of mutations in the SMARCB1 gene has been reported in PES cases. Although deletion could be seen in both PES and MRT, the finding of heterologous deletion is more common in PES, but rare in MRT, which typically demonstrates homozygous deletions in SMARCB1. The lack of mutation and deletion in a HN PES warrants study to further investigate alternative mechanisms, such as epigenetic silencing, intronic mutations, RNA editing, or post transcriptional control, resulting in loss of SMARCB1 expression in PES.
Category: Head & Neck
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 205, Monday Morning