CYSTIC TUMOR IN A 4 MONTH OLD MALE

CLINICAL HISTORY

A 4‐month‐old male infant with an uneventful antenatal and natal history, presented with persistent vomiting and recurrent right‐sided focal seizures of one month duration. He was seen by a pediatrician and found to have wide bulging fontanels and a large head circumference (46 cm, above 90 percentile), with limited movement in the right upper limb. Brain US showed a left sided brain mass. Brain MRI was requested and showed a large mainly cystic septated mass, with a thin non‐enhancing wall and a relatively large vividly enhancing mural nodule. The mass involved the left parieto‐occipital lobes and was deeply located in close relation to the left lateral ventricular trigone. Extensive associated white matter edema was noted. He underwent emergency craniotomy and complete resection of the tumor was attempted. Post operative brain MRI showed a large cystic lesion measuring about 4.7 × 5 cm at the site of surgery with no evidence of enhancement. He was seizure free with no weakness post craniotomy.

NEURO‐RADIOLOGY

Pre operative brain MRI of axial T1 weighted image (WI) showed a large mainly cystic mass in the left parieto‐occipital lobes with marked surrounding white matter edema (Figure‐1a). There was a hyperintense solid nodule at the medial part of the mass in close relation to the left lateral ventricular trigone. Its relation to the choroid plexus could not be assessed. The cystic part of the mass was septated. The solid nodule showed vivid enhancement after contrast administration (Figure‐1b) while the walls of the cystic component did not. Axial T2 WI of the cystic part of the mass contained CSF intensity fluid while the solid part of the mass was hypointense (Figure‐1c).

Figure 1.

MICROSCOPIC PATHOLOGY

Sections examined from the pathology material revealed a papillary tumor (Figure‐2). The papillae were lined by a single layer of cuboidal to columnar cells (Figure‐3) with acidophilic cytoplasm, and occasional cells displaying clear cytoplasm. The nuclei showed minimal atypia (Figure‐3). Mitotic activity was brisk and several high power fields contained more than one mitotic figure (Figure‐4). Calcifications were identified in the cores of several papillae. In a single focus; invasion into the brain parenchyma was identified with surrounding reactive astrocytes. Adjacent normal choroid plexus was seen. S‐100 protein was negative in the tumor cells, but positive in the normal choroid plexus. Transthyretin was positive in the tumor cells (Figure‐5). MIB‐1 immunostain revealed high proliferative index (Figure‐6). What is the diagnosis?

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

DIAGNOSIS

Cystic atypical choroid plexus papilloma, WHO grade II.

DISCUSSION

Choroid plexus tumors are rare tumors, seen mostly in children, where they comprise 2–4% of all brain tumors in the pediatric age group (9). The most common variant is choroid plexus papilloma (CPP), corresponding to WHO grade I tumors. Morphologically they grow in a papillary pattern with fibrovascular cores lined by a single layer of cuboidal to columnar cells with minimal pleomorphism, and have a sparse mitotic count. Complete surgical resection is the treatment of choice and is associated with an excellent prognosis. In contrast; choroid plexus carcinomas (CPC), correspond to WHO grade III, are aggressive tumors and have a dismal prognosis. They are characterized by areas of solid growth pattern, marked pleomorphism, increased mitotic count and necrosis. Brain invasion can be seen in all grades and per se, would not warrant a more aggressive behavior according to the WHO classification.

The presence of some tumors that are intermediate between CPP and CPC has only been recently included in the WHO classification. Patients with atypical CPP are significantly younger than other tumors (10). These atypical tumors show a papillary growth pattern with minimal pleomorphism. However; they tend to exhibit an increase in the mitotic count of ≥2/10HPFs (3). The presence of occasional features of malignancy as seen in CPC is accepted although not required for making this diagnosis. In addition, proliferative marker Ki67 and p53 staining are intermediate between the benign and the malignant counterparts (10). Surgical excision is the treatment of choice in these patients. Chemotherapy is preserved for cases with recurrence or metastatic development.

The cystic variant of choroid plexus tumors was first recognized in 1967(2). Since then, only a few cases have been reported 1, 4, 5, 7, 8. Many of these tumors are seen in infants and are considered congenital in some cases. Occasionally, these lesions are discovered during routine antenatal screening(5). Acute obstructive hydrocephalus can result in sudden death 4, 8.

Radiologically; there is a large cystic mass with or without a mural nodule, located in the medial portion of the cyst wall(9). The nodule enhances after contrast medium injection. However, in the absence of such nodules, the cyst wall enhances instead. The content of the cyst is identical to CSF. All cases described so far have been of CPP (1). Treatment included total excision of the mural nodule and the cystic wall which resulted in complete cure (1).

The radiological differential diagnosis for a cystic tumor with an enhancing mural nodule includes pilocytic astrocytoma, hemangioblastoma, pleomorphic xanthoastrocytoma, meningioma and ganglioglioma. In the absence of a tumor nodule, choroid cyst comes into the differential diagnosis(6). Pathologically; cystic CPP's without a mural nodule are lined by cuboidal and elongated columnar epithelium with atypical nuclei, increased cellularity and positive Ki‐67 immunostain(4). Another pathological differential diagnosis is papillary ependymoma, which shows GFAP strongly positive fibrillary cores in the absence of basement membrane. Yolk sac tumor is also an important consideration in this age group. However; these tumors are located in the midline, contain eosinophilic globules and are positive for α feto‐protein. As with all pediatric brain tumors, approach to management should be discussed within a multidisciplinary team. Choroid plexus tumors are extremely rare and calls for international collaboration should be considered.

ABSTRACT

Cystic choroid plexus tumor is a rare variant of choroid plexus papilloma (CPP), reported mostly in infants. It is associated with the development of acute hydrocephalus in many cases. The presence of atypical CPP has recently been recognized by the WHO as a grade II tumor with increased mitotic activity. We are reporting a case of a 3.5 month infant who presented with seizures and features of increased intracranial pressure. He was found to have cystic atypical choroid plexus papilloma.