ZBTB16 is a sensitive and specific marker in detection of metastatic and extragonadal yolk sac tumour

Aims Accurate histological diagnosis and classification of germ cell tumours (GCTs) is key to informing successful therapeutic and surveillance strategy. The modern therapeutic approach for yolk sac tumour (YST) is highly curative. Because YST takes on a large morphological spectrum, it can be confused for other GCT subtypes as well as somatic carcinomas, particularly when YST presents in an extragonadal or a metastatic setting. Currently available immunohistochemical markers are limited by suboptimal sensitivity and specificity. We reported recently that ZBTB16 is a sensitive and specific marker for testicular YST. ZBTB16 is absent in other GCTs and in most common somatic carcinomas, including those of gastrointestinal, pancreatobillary, respiratory, genitourinary and gynaecological tracts. The purpose of this study is to investigate the diagnostic utility of ZBTB16 in the settings of metastatic and extragonadal YST. Methods and results We studied 32 archived metastatic and four extragonadal primary YSTs as well as 51 somatic malignancies for their immunohistochemical expression of ZBTB16. For comparison, α‐fetoprotein (AFP) and glypican‐3 were also studied in parallel. Our results demonstrated an overall sensitivity of 91.6% for ZBTB16 in detecting metastatic and extragonadal YSTs. The non‐YST elements (teratoma and embryonal carcinoma) in 15 YST‐containing metastatic mixed GCTs were non‐reactive. With the exception of occasional myoepithelial cells of salivary gland carcinoma, all the 51 somatic malignancies were negative for ZBTB16. Conclusions ZBTB16 is a sensitive and specific marker for YST and is diagnostically superior to AFP and glypican‐3 in metastatic and extragonadal settings.