| Context: SALL4 is an immunohistochemical marker traditionally used to support the diagnosis of germ cell tumors (GCT). In non-germ cell neoplasms, SALL4 expression is associated with stem-cell-like or dedifferentiated phenotypes. DICER1 mutations are key molecular drivers of a subset of gynecologic neoplasms, including moderately to poorly differentiated Sertoli-Leydig cell tumors (SLCT), rhabdomyosarcoma, and adenosarcoma. However, SALL4 expression within DICER1-mutated gynecologic neoplasms remains underrecognized, representing a potential diagnostic pitfall. Design: A systematic review of the PubMed literature (2020–2024) was performed to identify gynecologic neoplasms with documented DICER1 mutations and SALL4 expression. Findings were combined with a previously unreported institutional case of an ovarian poorly differentiated SLCT harboring a DICER1 mutation located at RNase III domain and exhibiting SALL4 expression. Molecular confirmation of the DICER1 mutation was performed using the MSK-IMPACT gene panel. Results: Seven SALL4-positive DICER1-mutated gynecologic neoplasms were identified (n=6 literature; n=1 institutional), involving ovary (42.9%; n=3), uterus (42.9%; n=3), and fallopian tube (14.3%; n=1). Tumor types included uterine sarcomas (42.9%; n=3), embryonal rhabdomyosarcomas (42.9%; n=3), and poorly differentiated SLCT (14.3%; n=1). Diffuse nuclear SALL4 expression was observed in the majority of cases (57.1%; n=4); the remaining cases (42.9%; n=3) demonstrated focal staining limited to rosettes or glands. Conclusions: SALL4 expression is not exclusive to GCT and may be observed in poorly differentiated SLCT, rhabdomyosarcoma, and adenosarcoma associated with DICER1 mutation. This may reflect a primitive immunophenotype associated with DICER1-driven oncogenesis. Awareness of this diagnostic pitfall is crucial to prevent misdiagnosis of SLCT as GCT. Distinguishing between these entities is essential for clinical management as GCTs are chemosensitive while SLCTs are not. |
