To the editor:

Lesions of the pineal region are diversified in histopathology. Intracranial epidermoid cysts account for 0.2–1.8% of all intracranial tumors [1], which are caused by abnormal changes in ectoderm cells during weeks 4–5 of embryonic development [2]. Germinoma is derived from embryonic germ cells. To the best of our knowledge, it has not previously been reported that epidermoid cyst and germinoma occurred sequentially in the pineal region of the same patient.

Case presentation

A 12-year-old male patient was admitted to the hospital due to recurrent headache lasting for 1 month. He was normally healthy and showed no remarkable neurological anomalies. Brain magnetic resonance image (MRI) (Fig. 1a–c) showed a cystic space-occupying lesion in the pineal region with obstructive hydrocephalus, which was (2 × 2 × 2 cm) 4.2 cm3 in size, T1 hypointense, T2 hyperintense and no enhancement.

Fig. 1
figure 1

Preoperative MRI on the first admission showed a hypointense cystic lesion in the pineal region without enhancement in T1-weighted a sagittal image and b axial image, and hyperintense in c T2-weighted axial image. The obstructive hydrocephalus was manifest. d Sagittal T1-weighted MRI obtained 6 months after the first operation showed the lesion was total removed in the pineal region. Contrast-enhanced MRI sagittal and axial images (e, f) on the second admission showed a homogeneous enhanced mass in the pineal region associated with obstructive hydrocephalus. Contrast-enhanced MRI sagittal and axial images (g, h) of 30 months follow-up after the second operation showed no evidence of tumor recurrence in the pineal region

Full size image

The patient received total resection of the lesion via a transcallosal interfornix approach in combination with third ventriculostomy. The lesion was cystiform with clear boundaries and appeared a characteristic “pearly tumor” with keratinous content in the cyst capsule. The surgical specimen was pathologically diagnosed as an epidermoid cyst (Fig. 2a). The postoperative course was uneventful (Fig. 1d).

Fig. 2
figure 2

Photomicrograph of the first surgery sample demonstrated a cyst consisting of stratified squamous epithelium with keratinous contents (a) (HE ×100), and negative immunochemical stained of PLAP (b) and OCT4 (c) (×400). This indicated that the first lesion was a pure epidermoid cyst

Full size image

The patient was followed up regularly every 6 months. Two years later, he was admitted to the hospital again with the main complaints of headache and diplopia. Neurologic examination revealed upward-gaze palsy (Parinaud’s syndrome). Brain MRI showed a recurrent spherical lesion in the pineal region, which was (3 × 3 × 3 cm) 14.1 cm3 in size, T1 and T2 homogeneously enhanced, and accompanied by recurrent obstructive hydrocephalus (Fig. 1e, f). Laboratory examination of serum tumor markers, including alpha-fetoprotein (AFP), beta human chorionic gonadotropin (β-HCG) and carcinoembryonic antigen (CEA), were negative. The second operation was done through the initial surgical approach. The ‘recurrent’ tumor has changed dramatically: the lesion was flesh pink color, soft texture, with rich blood supply but no envelope. Biopsy of the tumor revealed it as a germinoma through the intraoperative frozen pathological examination and sequentially immunohistochemistry staining (Fig. 3a–c). It was positive for placental alkaline phosphatase (PLAP), leukocyte common antigen (LCA), OCT4, CD117 and negative for glial fibrillary acidic protein (GFAP), AFP, EMA. Thereafter, the patient received an intraoperative direct third ventriculostomy to improve the obstructive hydrocephalus. One week after surgery, the patient received gamma knife radiosurgery at a local prescription dose of 15 Gy, followed by whole brain radiotherapy at a prescription dose of 26 Gy 1 month later.

Fig. 3
figure 3

Photomicrograph of the second operation specimen showing classical features of germinoma (a) (HE ×400). Histopathological features of germinoma: positive immunochemistry staining of PLAP (b) and OCT4 (c) (×400)

Full size image

After the second surgery, we had a suspicion that the first lesion might have been a mixed germ cell tumor containing a component of germinoma that could later return as a germinoma. Therefore, an additional immunohistochemical staining of the specimen obtained from the first surgery including the factors of PLAP and OCT4 (Fig. 2b, c) was done. The result was negative for both PLAP and OCT4, excluding the diagnosis of mixed germ cell tumor.

The 30-month follow-up showed that the clinical symptoms of the patient had disappeared. The patient led a normal life and is now a high school student with good academic records. Follow-up MRI showed no tumor recurrence (Fig. 1g, h).

Discussion

Tumors in the pineal region cover a wide spectrum of histological types and accurate pathological diagnosis is a critical reference for determining the need for postoperative chemoradiotherapy. It has been generally agreed that epidermoid cysts are benign lesions, which need no adjuvant therapy after total resection. However, intracranial epidermoid cysts may transform into malignant squamous cell carcinomas. Hamlat et al. [3] reviewed 52 cases of intracranial squamous cell carcinomas and found that 16 of them arose from the postoperative remnant of an epidermoid cyst. Was the pineal germinoma in our case malignantly transformed from an epidermoid cyst remnant of the first surgery? We believe it is impossible, because the histopathological type of the two tumors differed completely.

For the two tumors to have occurred sequentially in the pineal region of the central axis, metachronous germinoma should be considered. Intracranial metachronous germinoma has very rarely been reported in the literature [4], and almost all of the first tumor was a mature teratoma located in a child’s pineal region. The mechanism of oncogenesis of metachronous germinoma is unclear. It can be speculated that germ cell tumors in the pineal region may often arise from residual primordial cells in the process of embryonic development, and these cell components may grow metachronously over a long time. Is there a trigger which promotes the second tumor in the pineal region? Hirano et al. [4] presumed that the level of hormone changes in puberty may activate the dormant oncogenes of residual primitive cells, which then develop into a tumor. However, it seems to be ill-defined in our case whether an analogous mode of transformation or trigger existed.

The possibility might exist that the former tumor was not adequately sampled, and a minor germinoma component had been present. Nevertheless, the first pineal lesion was radically removed and the additional immunohistochemical examination was negative for both PLAP and OCT4. A thorough pathological examination of the first lesion could not find any signs of a germinomatous cells aggregation but only a typical epidermoid cyst.

The occipital transtentorial approach in the pineal region is more frequiently reported in the literature. In this case, the advantage of the transcallosal interfornix approach was that we could not only resect the tumor but also perform the third ventriculostomy directly. In this way, the obstructive hydrocephalus was relieved to avoid shunt placement and its complications.

Is there any necessity of follow-up after total resection of epidermoid cysts in the pineal region? It is usually considered that no radiological follow-up is needed for benign cysts, unless there are symptoms [5]. Nonetheless, malignant transformation of an epidermoid cyst is possible and a metachronous neoplasm has the potential to develop in this region, especially in pediatric patients. Thus, we believe that children should be closely followed up after initial resection of epidermoid cysts in the pineal region.