Pediatric Yolk Sac Tumors Research Articles

SALL4 is a useful marker for pediatric yolk sac tumors.

SALL4 is a zinc finger transcription factor that exerts its physiological role during embryo-fetal development. Analyses of SALL4 expression have shown its oncogenic role in precursor B-cell lymphoblastic lymphoma, acute and chronic myeloid leukemia, gastrointestinal, breast, and lung cancers. The aim of this study was to determine the immunohistochemical profile of SALL4 in pediatric yolk sac tumors (YSTs). Immunohistochemistry detection of SALL4 was performed in 22 cases of pediatric YSTs and 10 mature teratomas. The percentage of tumor cells stained was scored as 0, 1+ (1-30% cells), 2+ (31-60%), 3+ (61-90%), and 4+ (> 90%). To compare its sensitivity and specificity with Glypican-3 and α-fetoprotein (AFP), we also stained tumors from these cases for Glypican-3 and AFP. In contrast to AFP and glypican-3, SALL4 staining in more than 90% of the tumor cells was seen in all 22 pediatric YSTs (100% sensitivity) (P < 0.001 for both SALL4 vs. AFP and SALL4 vs. glypican-3). SALL4 is a sensitive marker for pediatric YSTs and it can be used to distinguish them from mature teratomas. SALL4 is likely to become a new and valuable biomarker for the diagnosis of pediatric YST.

RNA-binding protein LIN28 is a sensitive marker of pediatric yolk sac tumors.

RNA-binding protein LIN28 is involved in maintaining the pluripotency of embryonic stem cells. It has been detected in different types of testicular and ovarian germ cell tumors (GCTs), but its status in pediatric YSTs (yolk sac tumors) is still unknown. The aim of this study was to determine the immunohistochemical profile of LIN28 in pediatric YSTs. Immunohistochemistry detection of LIN28 was performed in 22 cases of pediatric YSTs and 10 mature teratomas. The percentage of tumor cells stained was scored as 0, 1+ (1-30% cells), 2+ (31-60%), 3+ (61-90%), and 4+ (>90%). To compare its sensitive and specificity with alpha-fetoprotein (AFP), we also stained AFP in 22 cases of pediatric YSTs and 10 mature teratomas in children. LIN28 staining was high in all 22 pediatric yolk sac tumor (2+ in 1, 3+ in 1, and 4+ in 20), and weak staining of LIN28 was seen in 1 of 10 mature teratomas (1+), 9 of 10 mature teratomas were negative expression. However, the expression of AFP in pediatric YST was lower compared with Lin28 (- in 1, 1+ in 8, 2+ in 12, and 3+ in 1), and weak expression of AFP was seen in 2 of 10 mature teratomas (1+), 8 of 10 mature teratomas were negative. LIN28 had higher intensity expression than AFP in pediatric YSTs (P<0.001). LIN28 is a sensitive marker for pediatric YSTs and it can be used to distinguish them from mature teratomas. LIN28 is likely to become a new and valuable biomarker for diagnosing of pediatric YST.

Detection of a metastatic lesion and tiny yolk sac tumors in two teenage patients by FDG-PET: report of two cases

We herein report the efficacy of FDG-PET for detecting yolk sac tumors in two teenage patients. One patient had a rare bone metastasis and the other had tiny recurrent lesions at the mediastinum. Both lesions were difficult to detect by conventional diagnostic modalities. In contrast, FDG-PET was very effective for detecting these lesions. Furthermore, the SUVmax of the lesion reflected the tumor activity, which was also suggested by the fluctuating values of serum alpha-fetoprotein (AFP), an established marker of yolk sac tumors. FDG-PET may be a useful procedure to detect tiny and metastatic, pediatric yolk sac tumors.

PAX8 and PAX2 Immunostaining Facilitates the Diagnosis of Primary Epithelial Neoplasms of the Male Genital Tract

PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Müllerian ducts and have recently emerged as specific diagnostic markers for tumors of renal or Müllerian origin. Little is known about their expression in the Wolffian duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Müllerian ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.

Transcription Factor GATA-6 is Expressed in Malignant Endoderm of Pediatric Yolk Sac Tumors and in Teratomas

Transcription Factor GATA-6 is Expressed in Malignant Endoderm of Pediatric Yolk Sac Tumors and in Teratomas

Transcription factor GATA-6 is expressed in malignant endoderm of pediatric yolk sac tumors and in teratomas.

Transcription factors GATA-4 and GATA-6 play critical roles in mammalian yolk sac differentiation and function. Previously, we showed that GATA-4 is a potential marker for malignant yolk sac endoderm in pediatric germ cell tumors. This highly malignant tissue can cause diagnostic problems because yolk sac components may be difficult to differentiate from other, especially immature, tissue types in teratomas. In the search for new molecular markers for germ cell tumors, we have surveyed GATA-6 expression in benign and malignant pediatric germ cell tumors using mRNA in situ hybridization and immunohistochemistry. GATA-6 was expressed in most yolk sac tumors examined and also in nonmalignant tissues including gut/respiratory epithelium, sebocytes, and neuroepithelium in mature and immature teratomas. Given that GATA-6 has not been discovered in sebocytes before, this finding was confirmed by immunohistochemistry of normal mouse samples, indicating a function for this transcription factor in the mammalian skin. Taken together, GATA-6 can be used to identify yolk sac components in pediatric germ cell tumors. Furthermore, it is also expressed in specific tissues in teratomas. GATA-6, together with GATA-4, can thus be used as a novel molecular marker in characterizing of pediatric germ cell tumors.

CURRENT MANAGEMENT OF PREPUBERTAL YOLK SAC TUMORS OF THE TESTIS

Over the last 3 decades, the management of pediatric yolk sac tumors of the testis has changed significantly. These changes reflect improvement in the treatment of testicular tumors in adults and children, such as the advent of platinum-based chemotherapy regimens. They also reflect increased understanding of the biology and natural history of prepubertal yolk sac tumors of the testis as a unique disease entity.

Transcription Factor GATA-4 Is Expressed in Pediatric Yolk Sac Tumors

Yolk sac tumors (YSTs) are malignant tumors that occur in the gonads of children and young adults, and at extragonadal sites in young children. The histological features of YSTs are variable and can be superimposed on other germ cell tumor histologies. Malignant endodermal cells within YSTs express alpha-fetoprotein, which can be detected in tumor tissue or serum. However, additional markers of endoderm differentiation would be beneficial for the classification of these tumors. Transcription factor GATA-4 regulates the differentiation and function of murine yolk sac endoderm, and its expression correlates with proliferation and cell survival in certain tissues. To see whether GATA-4 plays a role in human YSTs, we surveyed its expression in human germ cell tumors and cell lines. Northern analysis demonstrated expression of GATA-4 mRNA in four human germ cell tumor lines exhibiting yolk sac endoderm differentiation. GATA-4 protein was detected in eight of nine pediatric YSTs by immunohistochemistry. Three of five immature teratomas exhibited GATA-4 in neural blastematous cells and in cylindrical epithelium, whereas all 16 mature teratomas were devoid of GATA-4. We conclude that GATA-4 is a clinically useful marker of human YSTs and speculate that it may play a role in the maintenance of the malignant phenotype.