Two Male Infants each with a Cerebellar Mass

Clinical History and Imaging

We present 2 cases of cerebellar mass of male infants. Case 1 is a 15‐month‐old male infant presented with irritability, poor oral intake and vomiting. Brain MRI revealed a 5.2×4.4cm‐sized mass in the left cerebellar hemisphere. The tumor showed robust enhancement and a mixed solid and cystic architecture without intratumoral hemorrhage (Figure 1A). The elective tumor resection was performed through paramedian suboccipital approach. The tumor was huge and hypervascular but friable. The tumor was well‐demarcated and removed totally. The patient had no additional neurological deficit postoperatively. The baby received adjuvant chemotherapy. He has lived without neurological deficit or tumor recurrence for 17 months of follow‐up.

Figure 1.

Case 2 is a 16‐month‐old male infant who presented to emergency room for recurrent vomiting and lethargy. Brain MR imaging showed 4.9×4.8cm‐sized enhancing mass with internal hemorrhage in the left cerebellar hemisphere and obstructive hydrocephalus (Figure 2A). The tumor resection was performed through paramedian suboccipital approach. The tumor was whitish and soft but hypervascular. Postoperative brain MR showed 1.1×1.2cm‐sized residual tumor abutting tentorium cerebelli and transverse sinus. The patient underwent re‐operation for the removal of the residual lesion after 5 days. Finally, the tumor was removed totally. The patient received adjuvant chemotherapy. He has presented regular outpatient clinic without tumor recurrence until 25 months of follow‐up.

Figure 2.

Microscopic Pathology

Case 1: H&E stained section showed loosely arranged polygonal shaped tumor cells with hyperchromatic nuclei. There was a structure consisted of a central vessel surrounded by cuboidal tumor cells in a cystic space (Figure 1B). The tumor cells were positive for CD117 (c‐kit) (Figure 1C), and alpha‐fetoprotein (AFP) (Figure 1D). No reactivity for CD30 and ‐human chorionic gonadotropin (β‐HCG) and placental alkaline phosphatase (PLAP) was observed.

Case 2: H&E stained section revealed central blood vessels with surrounding rosette‐like arrangement of tumor cells (Figure 2B). Immunohistochemically, the Ki‐67 proliferation index was 71.15%. CD117 (Figure 2C), pan‐cytokeratins, and AFP (Figure 2D) were positive in the tumor cells. The tumor cells were negative for CD30, β‐HCG, PLAP, programmed death 1 (PD‐1), and programmed death‐ligand 1 (PD‐L1). What are the diagnoses?

Diagnoses

Yolk sac tumors in the cerebellum.

Discussion

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 4^th ventricle were reported. The present study reports two patients with YST arising from the cerebellar hemisphere. To date, only 6 cerebellar YST have been reported. The ages ranged 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. Radiological features of cerebellar YST are similar to medulloblastoma, but YSTs tend to have a better demarcation and mild peritumoral edema.

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.

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 without recurrence. In our patients, although the radiotherapy is deferred because of the young age of the patients, the patients attain progression‐free survival of 17 and 25 months, respectively. The prognosis of YST in the cerebellum of infants may not be 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 rare but should be considered if there is a well‐enhancing, clearly demarcated cerebellar mass is found in male, young infants, especially if of Asian ethnicity.