A 49 Year‐Old Woman with a Pineal Mass

Clinical History and Imaging Studies

A 49 year old woman with a remote history of borderline serous tumor of the right ovary presented with a history of headache, nausea and vomiting. MRI imaging of the brain showed mixed solid and cystic pineal region mass causing obstruction at the level of the cerebral aqueduct associated with marked hydrocephalus (figure 1a). The patient underwent a third ventriculostomy and pineal region tumor biopsy.

Figure 1.

 

Neuropathologic Findings

The tumor submitted for neuropathological evaluation consisted of multiple pieces of soft, tan and red tissue ranging in size from 0.2 × 0.2 × 0.2 cm in greatest dimension.

Microscopically the tumor has a distinctive papillary architecture (figure 1b and 1c). The lining tumour cells are columnar and display slight to moderate nuclear pleomorphism. Tumour cells nucleus has stippled chromatin and a small nucleolus. Mitotic activity is almost negligible. The stroma of the fronds contains variable amount of collagen. True rosettes are not identified. Of note is the presence of cells with a cytoplasmic clear vacuole or eosinophilic condensation of the cytoplasm.

The tumor cells are immunopositive for pankeratin, low molecular weight cytokeratin (LMWCK) (figure 1d), CK19 (figure 1e), CD56 (figure 1f), and focally positive for S100 (figure 1g). EMA showed focal dot like paranuclear positivity and GFAP was focally positive, mostly labeling the neuropil. The ki67 index was less than 2%. The tumor cells are immuno negative for synaptophysin, CK 7, CK 20, WT‐1, ER, PR and CEA. What is the diagnosis?

Diagnosis

Papillary tumor of the pineal region, WHO grade II–III.

Discussion

Papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor of the pineal gland and was originally described as a distinct clinicopathological entity by Jouvet in 2003 6. It has recently been classified as a new entity according to the 2007 WHO classification. The biological behavior appears to be variable and may correspond to a WHO grade II or III neoplasm but the exact histological grading criteria are yet to be defined 7.

These tumors are exclusively found in the pineal regions of children and adults. The age of onset of the reported cases ranges from 15 month to 67 years and there is a slight female predilection 2, 8. The most frequent presenting symptom is headache, which related to obstructive hydrocephalus 1, 4, 5, 8.

Neuroimaging studies consistently show mixed solid and cystic masses usually with heterogeneous contrast enhancement 3. Grossly, PTPR appear as well circumscribed and relatively large masses ranging from 2.5 to 4 cm. Histologically, PTPR is characterized by a papillary structures interspersed with more diffusely cellular areas. The papillary structures are comprised of fibrovascular core with variable amount of collagen and covered by multiple layers of cells. The tumor cells are cuboidal to columnar and have small, round to oval nuclei, stippled chromatin, small nucleoli and eosinophilic cytoplasm with distinct cell borders. Rosettes and perivascular pseudorosettes are often seen in the solid component. Nuclear pleomorphism and necrosis may be seen. Mitotic activity ranges from 0 to 10 by 10HPFs. Microvascular proliferation has not been identified. Hyalinized blood vessels have been described in some cases. Also, eosinophilic cytoplasmic inclusions are sometimes present and they are usually PAS positive and PAS‐D sensitive granules 1, 2, 5, 6, 7, 8.

PTPR differs somewhat from the other primary or metastatic pineal tumour with papillary features in its immunohistochemical profile. The most distinctive feature of its immunohistochemical profile is the reactivity to a broad spectrum of cytokeratin, including CK18, AE1/AE3, and Cam5.2. The tumor cells are also strongly positive for S100, CD56 and NSE. The tumour cells may show focal positivity for GFAP and synaptophysin. Focal membrane or dot‐like EMA staining can sometimes be seen. The Ki67 proliferative indices range from 0 to 10 % 2, 6, 7, 8. Ultrastructural analysis has shown a mixture of ependymal, secretory and neuroendocrine features of the PTPR cells 6, 7. Because of their morpho functional features, PTPR are thought to derive from specialized ependymocytes of the subcommissural organ located under the pineal gland 6.

The expected course of PTPR is uncertain and data on the outcomes of patients with this tumor are limited. Although the surgical resection is the accepted treatment of choice, the optimal management is yet to be established and radiotherapy is often necessary due to the high risk of local recurrence 1, 4, 5, 8.