Yolk sac tumors in the cerebellum.
Yolk sac tumor (YST), one of malignant non-germinomatous germ cell tumors, occurs almost exclusively in the pediatric population. The common age of diagnosis of YST is between 7 months and 3 years old (2). It is known that YST is predominantly develops in females.
Germ cell tumor (GCT) occurs mainly in the gonads. Extragonadal GCTs are relatively rare, and found in the midline of human body including sacrococcygeal area, mediastinum, retroperitoneum, and central nervous system. The anatomical distribution of extragonadal GCTs has been explained as follows. The primordial germ cells are located in the yolk sac endoderm during an early embryonal stage. Germ cells migrate toward the genital ridge. During the process, misplaced germ cells are eliminated. If they survive in ectopic locations and acquire neoplastic properties, they become neoplastic germ cell with totipotentiality (4).
The most common pathologic diagnosis of primary intracranial GCT is germinoma. Intracranial GCTs have male predominance throughout all histological subtypes. Intracranial GCTs present commonly in the midline of the brain, such as in the pineal gland and suprasellar area (3). A few cases of GCTs in the cerebellar vermis and 4th ventricle were reported. YSTs are often found in the sites escaping midline of the brain, including basal ganglia, lateral ventricle, cerebral parenchyma, and cerebellar hemisphere. The present study reports two patients with YST arising from the cerebellar hemisphere. To date, only 6 patients of YST in the cerebellar hemisphere has been reported. The age distribution of the patients ranges from 15 months to 4 years. Interestingly, all reported patients were male, despite the fact that YSTs are more prevalent in females. As it is known, intracranial GCTs are prevalent in East Asia. Reported patients with cerebellar YSTs were all Asians, composed of four Koreans, three Japanese, and one Chinese.
Atypical teratoid/rhabdoid tumor (AT/RT) and medulloblastoma are considered as the most common tumors in the cerebellar hemisphere of infants. AT/RT usually presents as a huge mass involving the whole cerebellar hemisphere and vermis. AT/RT characteristically displays heterogeneous features in architecture. MR images of medulloblastoma show a mass with homogenous low signal intensity on T1-weighed images and slightly high signal intensity to gray matter on T2-weighted images. Gadolinum-enhanced T1-weighted images reveal a heterogeneously enhanced mass. Radiological features of cerebellar YST is similar to medulloblastoma, but YSTs tend to have a better demarcation and mild peritumoral edema.
The diagnosis of YST was confirmed by the pathologic examination in our patients. Schiller-Duval body is the typical histological finding, a glomerulus-like structure composed of a monolayer of cubic or columnar epithelial neoplastic cells surrounding the capillaries, thin-walled blood sinus or small venous vessels. Another diagnostically helpful finding is the presence of PAS-positive/diastase-resistant, hyaline eosinophilic globules in the cytoplasm and intercellular basement membranes arranged as thick, longitudinal bands of eosinophilic material. Immunohistochemically, cytoplasmic reactivity for AFP (positive in yolk sac tumor, usually negative in embryonal carcinoma) and nonreactivity for CD30 (positive in embryonal carcinoma, negative in yolk sac tumor) and Octamer-binding transcription factor 4 (OCT4, positive in embryonal carcinoma, negative in yolk sac tumor) is characteristic (1).
Alpha-fetoprotein is normally synthesized by yolk sac endoderm, fetal hepatocytes and intestinal epithelium. Marked elevations of AFP levels imply the presence of YST elements (3). Serum and cerebrospinal fluid AFP reflects the amount of tumor mass. Serial measurement of serum AFP level (sAFP) is also important for monitoring of the response to treatment, detecting recurrence, and predicting prognosis. In our two patients, initial impressions were not YSTs and sAFP were not measured before operations. High levels of sAFP were checked postoperatively after the presumptive diagnosis of YST based on the frozen biopsy. In case 1, we measured the preoperative sAFP using the remaining serum in the laboratory collected before the tumor resection, as it was 55,748 ng/mL. Postoperatively, sAFP decreased to 10,999 ng/mL. In case 2, sAFP checked in immediate postoperative day was 24,765 ng/mL. The level fell to 361.7 ng/mL after 2 days. During the chemotherapy, sAFP decreased gradually and normalized in both patients.
The treatment of non-germinomatous germ cell tumor (NGGCT) is a combination of chemotherapy and radiotherapy (1). If surgical resection of tumor is feasible, it is recommended that the maximal surgical resection be performed. The prognosis of NGGCTs is very poor. Although recent series show more promising results, treatment of intracranial YST is still challenging. Compared to germinoma, NGGCTs are less radio-sensitive and have less satisfactory results after radiotherapy. Therefore, the multimodal approach is important.
In the previous and present cases, six of eight patients were alive at the last follow-up without recurrence of the tumor. In our patients, although the radiotherapy is deferred because of the young age of the patients, the patients attain progression-free survival of 17 months and 25 months, respectively. It seems that the prognosis of yolk sac tumor in the cerebellar hemisphere of infants is not so dismal. However, it is hard to generalize: the number of cases is very small and the follow-up period for all reported patients was not long, less than 5 years.
Intracranial YST is a rare entity. If a well-enhancing, clearly demarcated mass is found in the cerebellar hemisphere of male, young infants, especially of Asian ethnicity, YST should be considered as differential diagnosis.
Contributed by Eun Jung Koh, MD; Seung-Ki Kim, MD, PhD; Sung-Hye Park, MD, PhD; Ji Yeoun Lee, MD, PhD; Kyu-Chang Wang, MD, PhD; Ji Hoon Phi, MD, PhD