SALL4 is a useful marker in the diagnostic work-up of germ cell tumors in extra-testicular locations.

We evaluated the impact of SALL4 immunostaining on the diagnosis of non-testicular germ cell tumors in clinical practice. We retrieved cases of six mediastinal, five retroperitoneal, and eight central nervous system tumors that were diagnosed as extra-testicular germ cell tumors (GCT) as well as 20 location-matched non-GCT. Each tumor we stained immunohistochemically for PLAP, OCT3-4, CD117, CD30, FP, -HCG, glycipan-3, SALL 4, AE1-AE3, EMA, CK7, CK20, CD45, TTF1, vimentin, and GFA. The results were assessed independently by two experienced pathologists. In 18 of 19 cases (95 %), SALL4 was strongly expressed, either homogenously (16 cases) or focally (two cases). All other GCT markers (PLAP, OCT3-4, CD117, CD30, FP, -HCG, and glycipan-3) were expressed with a lower frequency (21-69 %). The specificity of SALL4 was 100 % in our series. SALL4 should be part of the first panel of antibodies for the diagnosis of a midline tumor (mediastinal, retroperitoneal, or pineal) in patients under the age of 40 years. We also recommend that SALL4 be used in the diagnostic work-up of undifferentiated tumors in any location and in patients of any age. When a tumor is SALL4 positive, in case of need the diagnosis of germ cell tumor can be further confirmed using additional conventional markers.