Management of Pineal Region Tumors

The pineal gland develops during the second month of gestation as a diverticulum in the diencephalic roof of the third ventricle. It is flanked by the posterior and habenular commissures in the rostral portion of the midbrain directly below the splenium of the corpus callosum.  

Pineal tumors constitute 3-8% of pediatric brain tumor & 1% of brain tumors in adults.Germinoma is the most common tumor of Pineal tumor ( about 20 to 40%), followed by astrocytoma, teratoma and Pinealoblastoma.

Germ cell tumors, Ependymoma and Pineal cell tumors metastasize easily through the CSF ( “drop metastasis”).

Pineal region is situated at the posterior aspect of 3rd ventricle. Pineal stalk comprises of Posterior commissure and Habenular commissure. Many structures are situated in this region. Tectum of the mid brain and quadrigeminal plate ( superior and inferior colliculi) are situated beneath the Pineal gland. Splenium of the corpus callosum is situated above this gland. The CSF space around Pineal gland is known as Quadrigeminal Cistern.
Pineal region tumors are derived from cells located in and around the pineal gland. 

So, many types of lesions may be seen in the Pineal region:

1.Tumors arising from the Pineal Gland are tumors of neuroepithelial tissue & classified as Pineal Parenchymal Tumors (According to the revised WHO-2007 classification of CNS tumors: i. Pineocytoma, ii. Pineoblastoma, iii. Pineal parenchymal tumor of intermediate differentiation, iv. Papillary tumor of the Pineal region)
                   

                       Pineocytoma ( or Pinealcytoma) is well differentiated, arises from pineal                                                             epithelium.WHO Grade I, intense homogeous enhancement

                       Pinealoblastoma ( or Pinealblastoma) is malignant, WHO Grade IV,is a form of                                                   primitive neuroectodermal tumor (PNET), most often affects children, has                                             predilection for CSF dissemination, Lobulated, heterogenous enhancement
                        Both are radiosensitive 

2.Tumor from rests of germ cells: Germ Cell Tumors: Germinomas, Embryonal carcinoma, Endodermal sinustumor (Yolk sac tumor), Choriocarcinoma, Teratoma
                      Germinomas: Malignant
                      Non-germinomatous germ cell tumors (NGGCT); Embryonal carcinoma,                                                         choricarcinoma, & endodermal sinus tumor( also known as yolk sac carcinoma)                                    are usually malignat except Teratoma ( mature & immature)

3.Tumors from the glial cells ( Glial cyst or Pineal cyst, tectal Plate glioma which are usually pilocytic astrocytomas)

     Pineal Cyst
              Usually an incidental finding (ie,seen on about 4% of MRI of the patients who are not                                                                                       symptomatic due to lesion in the Pineal region)
              Commonly intra-pineal glial-lined cysts of less than 1 cm diameter.
              Etiology is not clear,  but considered as nonneoplastc and benign, and may be due to                                         ischemic glial degeneration or due to sequestration of the pineal diverticulum.
               It may contain clear or xanthrochromic or hemorrhagic fluid. Rarely it may enlarge &                                     become symptomatic as other Pineal masses. So, if size is less than 2cm, follow with                           annual imaging. If large & symptomatic: surgery( shunt, ETV,  cyst excision,                                       stereotactic or endoscopic aspiration)

4.Tumors from the Ependymal lining; Ependymoma

5. Tumors/lesions from arachnoid cells: Meningiomas, Arachnoid cysts

6. Tumors from sympathetic nerves: Chemodectomas

7. Tumors from remnant of ectoderm: Epidermoid, Dermoid

8. Tumors originating from elsewhere in the body: Metastasis (Absense of Blood Brain Barrier in the                                                                                                      Pineal land makes it susceptible site                                                                                                          for hematogenous metastasis)
9. Lesions which mimic tumors
                                      Vascular: Vein of galen aneurysm
                                      Infection: Neurocysticercus, Tuberculoma


Clinical Features of Pineal region masses
           Generally manifest in 3 ways: 
                           1. Symptoms of increased intracranial pressure from hydrocephalus 
                           2. Direct Brainstem and cerebellar compression
                           3. Endocrine dysfunction 


How to approach a case with a mass in Pineal Region? 

Take History:  History may give features of raised ICP like Headache, vomiting, or symptoms due to                         mass in the posterior third ventricular region: visual disturbances, lethargy, memory                             disturbances. 
Do Clinical examination : In infants: increased head circumference, seizures
                                          In boys with choriocarcinoma or germinomas with syncytiotrophoblastic                                                         cells: Precocious Puberty ( due to leuteinizing hormone-like effects                                                       of beta-hCG secreted in CSF
                                          Papilloedema
                                          Parinaud's syndrome (upward gaze palsy, converegence or retracction                                                                    nystagmus,light-near pupillary dissociation)
                                          Sylvian Aqueduct Syndrome (from further midbrain compression):                                                                      Paralysis of down-gaze or horizontal gaze, can be superimposed                                                            on Parinaud's syndrome
                                           Dorsal Midbrain Compression or infiltration can lead to lid retraction (                                                                Collier's sign) or ptosis. May appear as setting sun sign.
                                           Diplopia if 4th cranial nerve palsy.
                                           Ataxia
                                           Radiculopathy or myelopathy due to drop metastasis

Sometimes Blood & CSF investigations may give some clue to the diagnosis: 
       Germ cell tumor (GCT) may give rise to tumor markers in CSF
                   beta-human chorionic gonadotropin ( beta-hCG) is elevated in CSF in choriocarcinoma                                                and in about half of germinoma cases.
                   Alpha-fetoprotein (AFP) is elevated with endodermal sinus tumor, embryonal carcinoma                                              and immature teratoma.
                   Placental Alkaline Phosphatase (PLAP) is elevated in CSF & Serum of intracranial                                                      Germinomas. 
       CSF may be collected by ventricular tap if lesion is large or through Lumbar Puncture if lesion is                   small & if there is no risk of herniation, if a patient presents with hydrocephalus and                             patient is operated for CSF diversion procedure  like shunt or ETV then CSF should be                         collected and sent for tumor markers. 
                                   Although tumor markers alone are not usually sufficient for making a diagnosis                                    of a pineal tumorsince many of these tumors are mixed cell type.n But, when                                        positive, tumor marker can be followed serially to assess treatment and to                                              look for recurrence.
                  
Neuro-radiological evaluation : MRI of the brain with contrast with MR spectroscopy. It may                           diagnose neurocysticercus or tuberculoma.
              Some other investigations may be required if features are suggestive of systemic metastasis.
              MRI of cervical, dorsal & Lumbosacral spine to assess for drop metastasis.

Treatment:
Ideal situation is to know the histopathology of the lesion. o, ideal treatment is surgical excision followed by adjuvant therapy.But optimal management strategy is not to harm the patient. Pineal occupies a deep position near the geometric center. Since it is situated in the eloquent area of the brain and in close proximity to the splenium, superior colliculus and hypothalamus and close relation with the deep venous system including Vein of Galen, a judicious decision should be taken before operating the patient.
 
1. Observation & annual MRI if a lesion is asymptomatic as an incidental pineal cyst of less than 1              cm,
 
2. Radiosurgery: New modality of treatment , if tumor is less than 3 cm in size.
 
3. Surgery:
  Ventriculo-peritoneal shunt,
  Endoscopic Third Ventriculostomy (ETV),
  Endoscopic cyst excision,
  Computer Assisted Cisternal Endoscopic Approach (CACE): supracerebellar infratentorial approach
  Stereotactic or Endoscopic aspiration
  Craniotomy and Micro-neurosurgical excision of the mass:
               Midline infratentorial supracerebellar approach ( Horsley & Krause as refined by Stein)
                     Oppenheim & Krause in 1913 reported First successful removal of Pineal tumor.
                     Krause in 1926 reported 3 cases of infratentorial approaches without operative mortality
                           
               Occipital transtentorial approach ( Poppen's)
               Transcallosal approach : Dandy 1921
        The extensive variety of histologic subtypes found in the pineal region makes it imperative to             establish a tissue diagnosis. Aggressive Microneurosurgical resection followed by adjuvant                 therapy is mainstay of management.

4.Radiotherapy & Chemotherapy
 
If Biopsy is Germinoma: Radiotherapy and Chemotherapy
                    Germinomas are very sensitive to radiotherapy and chemotherapy. "Test dose" radiation                                 or "Trial XRT" of 5 Gy in a uniformly enhacing germinoma: if shrinks. Then XRT                               without surgery ( controversial as 36-50% of Pineal tumors are benign &                                                radioresitant}
 

Sources:

Mark S. Greenberg, Handbook of Neurosurgery, 7th ed., Thieme

emedicine.medscape.com/article/249945-overview ( Pineal Tumors, Author:Jeffrey N Bruce, MD; Chief Editor: Brian H Kopel)

Tandon PN, Ramamurthy R, Jain PKN. Ramamurthy & Tandon's Manual of Neurosurgery, Publisher: Jaypee

Jeffrey N.Bruce. Pineal Tumors. Chapter in Youmans Neurological Surgery, 6th ed. , H.Richard Winn, Elsevier Saunders,1359-1372.