60 Pineal Region Tumor

Claude-Edouard Chatillon, José-Luis Montes, and Jean-Pierre Farmer

Fig. 60.1 Computed tomography scan of the head without contrast at the level of the pineal gland.

Fig. 60.2 Artist’s rendering of stereotactic approaches to pineal region tumors. (A) Low frontal (precoronal) approach avoids the internal cerebral veins above the tumor. (B) The lateral pineal pulvinar approach, which is lateral to the deep veins, is depicted. (From Sekhar L, Fessler R. Atlas of Neurosurgical Techniques: Brain. New York: Thieme Medical Publishers; 2006:570–571. Reprinted with permission.)

Clinical Presentation

An 18-year-old right-handed man, otherwise healthy, presents to your clinic with a one-week history of progressively increasing headaches.

These are worse in the morning and are associated with nausea and vomiting.

There are no other systemic symptoms.

Physical examination is unremarkable.

A computed tomography (CT) scan of the head is obtained and shown in Fig. 60.1.

Questions

Interpret the CT scan.
Provide a detailed differential diagnosis of pineal region tumors.
Describe the typical presentation patterns of pineal region tumors.
What studies would you order?

In this case, tumor markers in the serum and cerebrospinal fluid (CSF) are negative.
Describe the different management options – their pros and cons and approach details.
Describe some adjuvant treatment measures for pineal tumors.
What is the prognosis for pineal region tumors?

Answers

Interpret the CT scan.

The CT scan shows a homogeneous and slightly hyperdense mass in the pineal region with mild dilatation of the ventricles.

Provide a detailed differential diagnosis of pineal region tumors.

Differential diagnosis is described below.1,2

Germ cell tumors (GCTs)

More frequent in children (75% in teens, 95% in younger than 33 years old)

Male-to-female ratio is 2:1.

They represent about one third of cases of pineal tumors.

Half the cases are germinoma.

On imaging studies: They engulf the pineal gland and are hyperintense to gray matter.

World Health Organization (WHO) classification ³ consists of

Germinoma

Embryonal carcinoma

Yolk sac tumors (endodermal sinus tumors)

Choriocarcinomas

Teratomas

Mature

Immature

With malignant transformation (carcinoma or sarcoma)

Mixed germ cell tumors

Pineal cell tumors

They represent about one quarter of cases of pineal tumors.

More frequent in young adults

Male-to-female ratio is 1:1.

Genetic predisposition in Rb mutations (trilateral retinoblastoma)

Pineoblastoma: Most are large, greater than 3 cm with peripheral calcifications. Usually associated with obstructive hydrocephalus.

Pineocytoma: enhancing, well-circumscribed pineal tumor with calcifications that rarely extend into the 3rd ventricle

Glial tumors

They represent about one quarter of cases of pineal tumors.

They arise from midbrain tectum or thalamus, rarely from the pineal gland.

They include ependymoma, astrocytoma, oligodendroglioma, and glioblastoma.

Other miscellaneous pathologies include

Meningioma

Lymphoma

Metastasis

Sarcoidosis

Infectious agents (tuberculosis, Whipple disease, etc.)
Describe the typical presentation patterns of pineal region tumors.
- Several presentation patterns have been described.¹
- Increased intracranial pressure
  - Morning headaches, nausea, vomiting, papilledema, obtundation, and extraocular muscle (EOM) dysfunction
- Direct brainstem compression
  - Parinaud syndrome (superior tectum involvement)
  - Down-gaze palsy, ptosis (periaqueductal gray or third nerve involvement)
  - Rare cases of “tectal deafness” (inferior colliculus involvement)
- Direct cerebellar compression
  - Ataxia, dysmetria (superior cerebellar peduncles or cerebellorubral fibers involvement)
- Hydrocephalus
- Endocrine dysfunction
  - Precocious pseudopuberty (male patients with beta human chorionic gonadotropin [β-HCG] producing tumors)
  - Hypothalamic dysfunction
- Pineal apoplexy
  - Acute presentation of aforementioned symptoms
What studies would you order?
- CT scan – may also be ordered with contrast.¹ Look for
  - Calcifications
  - Hydrocephalus
  - Vascularity
- MRI scan to look for¹
  - Signal characteristics of the tumor
  - Anatomical relationships and planes
  - Displacement of the deep venous structures
- Serum and CSF tumor markers¹
  - May help identify GCTs
  - Positive α fetoprotein (AFP) present in
    - Yolk sac tumors
    - Embryonal cell carcinoma
    - Immature teratoma
  - Positive β-HCG present in
    - Choriocarcinoma
    - Germinoma with syncytiotrophoblasts
    - Embryonal cell carcinoma
  - Positive placental alkaline phosphatase present in:
    - Germinoma
    - May be positive in all GCTs
  - Absence of markers does not exclude the diagnosis of GCT
  - One may have a mixed GCT (i.e., it may have multiple tumor components expressing different markers).
- For staging purposes, all patients with malignant pineal cell tumors, GCTs, and ependymoma will need a spinal MRI and CSF cytology (which is rarely positive, even when seeding is present).
Describe the different management options – their pros and cons and approach details.
- Management of hydrocephalus depends on the clinical status and subsequent definitive treatment plan.¹ Options include
  - Close observation while awaiting surgery
  - Ventriculostomy or external ventricular drain
  - Endoscopic third ventriculostomy (ETV)
  - Ventriculoperitoneal (VP) shunt
- One of the goals of management includes obtaining tissue diagnosis.
  - This may not be necessary if malignant GCT markers are present.
  - Stereotactic biopsy or open biopsy/resection approached may be used.
- Stereotactic biopsy^1,4
  - Pros and cons include
    - Relative ease of performance
    - Less complications
    - Risk of inadequate sampling in mixed GCTs
    - Report of seeding in pineoblastoma
  - Approaches include precoronal with low frontal entry point, the pathway along the antero-latero-superior portion of the tumor, inferior and lateral to internal cerebral vein, parieto-occipital and postero-latero-superior (for tumors with postero-lateral extension) (Fig. 60.2).
  - Serial biopsies are desirable.
  - Sample areas with different MRI signal.
- Endoscopic biopsy¹
  - May perform ETV and biopsy during the same procedure
  - Cons include
    - Flexible endoscope or a second burr hole is required.
    - Risk of intraventricular hemorrhage
    - Obliteration of the field of view may occur.
    - Difficult to control the endoscope in inexperienced hands
- Open biopsy with possibility of resection^1,5
  - Pros and cons include
    - More confident diagnosis
    - Reduction of tumor burden
    - Control of bleeding
    - Possibility of complete resection (teratoma, pineocytoma)
    - Increased morbidity of a major surgical procedure
  - Common approaches⁵
    - Infratentorial supracerebellar
    - Occipital transtentorial
    - Transcallosal interhemispheric
    - The best approach depends on individual tumor characteristics and the surgeon’s familiarity with the approach.
  - Infratentorial supracerebellar approach¹
    - Extraaxial pathway to the tumor via a midline approach
    - Inferior to the deep veins
    - Sitting position, which places gravity at work to the surgeon’s benefit
    - Risks include blood pooling, cerebellar retraction, awkward surgical positioning, air embolism, and venous sinus injury.
  - Occipital transtentorial approach
    - ¾ prone (or sitting) position, oblique trajectory
    - Excellent exposure of the quadrigeminal plate
    - Also places gravity at work to the surgeon’s benefit
    - Disadvantages include working around deep veins, occipital lobe retraction, and risk of visual field deficit
  - Transcallosal interhemispheric approach
    - Prone (or sitting) position, callosotomy centered around the tumor and should be limited to less than 2 cm
    - Disadvantages include working around deep veins, bridging veins may limit exposure, and risk of disconnection syndrome.
    - May be combined with the occipital transtentorial approach
Describe some adjuvant treatment measures for pineal tumors.
- One possible regimen consists of
  
  40 Gy to the ventricular system +15 Gy to the tumor bed
  
  35 Gy to the spine empirically or if there is evidence of radiographic metastases or positive CSF cytology
  
  Reduced craniospinal radiation doses in combination with chemotherapy is currently the standard treatment for germinoma in many centers.2,6–8
- Chemotherapy (usually combined with radiation) is used in germinoma, nongerminomatous GCTs (NG-GCTs), germinoma with syncytiotrophoblastic cells, and recurrent or metastatic germinoma or pineal cell tumors.
- Regimens include the Einhorn regimen⁹ (also used in testicular cancer), which consists of cisplatin, vinblastine, bleomycin, or etoposide replacing vinblastine–bleomycin to avoid pulmonary toxicity. Other commonly used regimens include for germinoma cisplatin, carboplatin, and etoposide. For pineoblastoma and NG-GCTs, it includes vincristine, cisplatin, cyclophosphamide, and etoposide.⁹
- Radiosurgery may be useful in the treatment of pineocytoma, but not in malignant pineal cell tumors or GCTs. It is limited to tumors smaller than 3 cm.^1,10
What is the prognosis for pineal region tumors?
- Prognosis is dependent on histologic diagnosis.¹
- In germinoma, the long-term survival rate is 90% with RT. In a study of 36 patients with germinoma by Hardenbergh et al.,¹¹ low-dose radiation was given to the tumor and neuraxis as well as a boost dose to the tumor bed. The 5-year disease-free survival rate was 97%. Poor prognosticators included positive CSF cytology for tumor cells and increased β-HCG levels.²
- In NG-GCT, the 5-year survival rate with RT was 36%.¹ The 2-year survival with chemotherapy was 62%. There was a 10% mortality rate from toxicity of chemotherapeutic agents¹
- In pineocytoma, a small series of four patients was studied by Tsumanuma et al.¹² The patients underwent total or subtotal resection with a mean survival rate of 8 years.¹²
- In pineoblastoma, Lee et al. reviewed a series of 34 patients, revealing a mean survival rate of 25 months after gross total resection and RT.¹³