Ch42 Lymphomas, Histiocytic Tumours, Germ cell tumours & Tumours of the Sellar Region

Question 1

What is the difference between primary and secondary lymphoma?

Answer 1

Primary lymphoma starts in the CNS. Secondary lymphoma has metastatic spread of systemic lymphoma to the cerebral parenchyma. They are pathologically identical but primary tends to be more in the parenchyma and secondary has more leptomeningeal involvement.

Question 2

What are the specific types of primary CNS lymphoma?

Answer 2

Diffuse large B cell lymphoma (most common) Immunodeficiency-associated CNS lymphoma - AIDS related - EBV diffuse large B cell Intravascular large B-cell lymphoma Miscellaneous rare lymphomas in the CNS -low grade B-cell lymphomas -T-cell & NK/T-cell -anaplastic large cell Extranodal marginal zone lymphoma of ‘mucosa-associated lymphoid tissue’ (MALT lymphoma) of the dura

Question 3

What are the characteristic sites for lymphoma?

Answer 3

Corpus callosum Basal ganglia Periventricular Cerebellum if infratentorial

Question 4

What are the histological features of lymphoma?

Answer 4

Tumour cells form perivascular cuffs which demonstrate multiplication of basement membranes (best demonstrated with silver reticulum stain). Cells stain for B-cell (CD20) and T-cells (CD3).

Question 5

What percentage of lymphoma patients have seizures?

Answer 5

30%

Question 6

How does lymphoma compare to glioma on MR spectroscopy?

Answer 6

Much higher choline to creatinine ratio in lymphoma Lipid peak also characteristic in lymphoma.

Question 7

What does normal brain MR Spectroscopy show?

Answer 7

Hunter’s angle with choline

Question 8

In MR Spectroscopy, what peak is seen before Choline?

Answer 8

Myoinositol

Question 9

What are the indications for operating on lymphoma?

Answer 9

Biopsy

Question 10

What does diffuse CD20 staining suggest?

Answer 10

B-cells

Question 11

What does diffuse CD3 staining suggest?

Answer 11

T-cell lymphoma

Question 12

What does this MR Spectroscopy show?

Answer 12

High choline (Cr should be just next to it but not even visible!)

Low NAA

High lipid/lactate peak (which is higher than would be expected from a HGG)

Suggestive of lymphoma

Question 13

What is intravascular lymphoma?

Answer 13

Formerly known as angioendotheliomatosis , there is no solid mass and all the lymphoid B-cells are found within the lumen of small vessels. Present with multifocal strokes. Needs a brain biopsy!

Question 14

How does PCNSL present?

Answer 14

Mental status change (encephalopathy / dementia)

Raised ICP

Seizure

Cranial nerve palsies

Question 15

What conditions increase the risk of PCNSL?

Answer 15

Immunosuppression (AIDS/ Transplant)

EBV

Rheumatoid / SLE / Sjoergren’s

Question 16

How do you investigate a patient with suspected PCNSL?

Answer 16

HIV test / CD4 count

LP

Bone marrow biopsy

CT-CAP

MRI brain and spine with contrast

Testicular USS if >60 years

Opthalmology (for uveitis)

Question 17

What are the CT findings you would expect with PCNSL?

Answer 17

Hyperdense lesion on non-contrast imaging

Fluffy border

Surrounding oedema with mass effect

Homogenous contrast enhancement

Question 18

What blood test is an independent prognosticator for lymphoma?

Answer 18

LDH - indicates rapid cell turnover

Question 19

What is the sensitivity of LP for suspected PCNSL?

Answer 19

10-20% when >10ml is taken. Repeating up to 3 times increases yield. Requires flow cytometry to provide information on tissue typing.

Question 20

What are the indications for surgery in PCNSL?

Answer 20

Biopsy

Question 21

How is PCNSL treated?

Answer 21

Whole-brain radiation

Chemotherapy (in non-AIDS cases) through IV and IT methotrexate

Rituximab (anti-CD20 monoclonal Ab)

Question 22

How are histiocytic tumours classified?

Answer 22

Histiocytes are mononuclear phagocytes (macrophages)

1. Malignant (histiocytic lymphoma)
2. Reactive (benign histiocytes)
3. Langerhan’s histiocytosis (unifocal, multifocal unisystem, multifocal multisystem)
4. Erdheim chester / Rosai-Dorfman
5. Histiocytic sarcoma

Question 23

What is unifocal langerhans cell histiocytosis?

Answer 23

AKA Eosinophilic granulomatosis / Histiocytosis X

Presents as a tender enlarging skull mass (Parietal>Frontal) in patients <20 years old

XR shows a non-sclerotic punched out lesion with sharply defined margins involving both the inner and outer table. No sunburst appearance so different from a haemangioma. If sclerotic margins think of an epidermoid

CT is helpful if you only have an XR

Question 24

How do you treat LCH?

Answer 24

Curettage if unifocal

Multiple lesions that have extracalvarial bony involvement are treated with chemo/radiotherapy. Very radiosensitive.

Question 25

What is Hand-Schuller-Christian triad?

Answer 25

Associated with LCH: DI (pituitary invasion), Exopthalmos (intraorbital tumour) and lytic lesions of the cranium.

Question 26

Which LCHs present like meningiomas?

Answer 26

Rosai-Dorfman and Erdheim chester

Question 27

What % of GCTs are synchronous i.e. in the pineal and sellar region?

Answer 27

13%

Question 28

What is the gender difference between GCTs?

Answer 28

In Males they occur most frequently in the pineal whilst in females, they are more common in the suprasellar region.

Question 29

What are the different types of GCTs?

Answer 29

Germinomas Non-germinomas Mixed

Question 30

What are teratomas?

Answer 30

GCTs composed of two or more germ cell layers (endo/meso/ectoderm) Mature teratomas contain mature skin / bone etc Immature teratomas contain fetal tissues Malignant transformation to carcinoma or sarcoma.

Question 31

Which germinomas are b-HCG positive?

Answer 31

Syncytiotrophoblastic variant. b-HCG is positive in 10-50% of all germinomas.

Question 32

Which GCTs are classically associated with raised bHCG?

Answer 32

Choriocarcinomas (also some germinomas)

Question 33

Which GCTs have high AFP?

Answer 33

Immature teratomas Yolk sac tumours Embryonal carcinomas

Question 34

Which GCTs have high pALP?

Answer 34

Germinomas - check the CSF and serum levels

Question 35

How should GCT tumour markers be used?

Answer 35

For monitoring response to treatment. Less useful for diagnosis and they may be mixed types. Note: if pALP is positive then no need for surgery and treat as a germinoma (chemotherapy and low dose RT with boost to the tumour).

Question 36

How would you manage a patient with a pineal lesion?

Answer 36

MRI brain and whole spine + contrast Serum / CSF tumour markers (bHCG, AFP & pALP) If hydrocephalus then ETV + biopsy If germinoma then chemo/rad All others resection

Question 37

What do craniopharyngiomas arise from?

Answer 37

Benign epithelial remnants of Rathke's pouch and therefore arise from the anterior pituitary.

Question 38

What are the histological findings in a craniopharyngioma?

Answer 38

Palisading epithelium, wet keratin and stellate reticulum associated with gliosis and rosenthal fibres. Cystic and solid components with cholesterol laden fluid, necrosis and calcification

Question 39

Which mutations are associated with craniopharyngiomas?

Answer 39

Adamantinomatous = beta-catenin Papillary = BRAF (usually solid)

Question 40

What are the age distributions of craniopharyngiomas?

Answer 40

Bimodal \<15 years or \>50 = adamantinomatous 40-50 years = papillary

Question 41

What is the blood supply to a craniopharyngioma?

Answer 41

Sup. hypophysial ACA ICA PCom

Question 42

What are the operative approaches to craniopharyngiomas?

Answer 42

Endoscopic transphenoidal Subfrontal / Fronto-temporal - approach is optico-carotid or subchiasmatic if the chiasm is pre-fixed and between the optic nerves (prechiasmatic) if post-fixed Transcallosal or translamina terminalis for tumours limited to the 3rd ventricle

Question 43

Describe a fronto-temporal approach for craniopharyngioma.

Answer 43

Pterional craniotomy Prox. sylvian dissection Identify ICA and Optic nerve - widely open the arachnoid and release CSF View both optic nerves, chiasm, lamina terminalis and follow ICA back to the bifurcation and release arachnoid between ACA and optics. Decompress cyst Dissect margins and protect the stalk / hypothalamus between the optic nerves and/or between optico-carotid window by mobilising carotid downwards Open lamina terminalis if 3rd ventricular component

Question 44

What are the management options for craniopharyngioma?

Answer 44

Shunting if hydrocephalus Cyst aspiration and ommaya reservoir insertion Bleomycin to the cyst through the ommaya Surgery of solid component Radiotherapy / SRS to residual

Question 45

Anatomical view / reach of the pterional approach

Answer 45

Question 46

What are the operative windows for transcranial craniopharyngioma resection?

Answer 46

Prechiasmatic Translamina terminalis Optico-carotid Carotid-oculomotor

Question 47

Anatomy of the opticocarotid window

Answer 47

Question 48

Which steroids should you prescribe post-op craniopharyngioma resection?

Answer 48

Both Dex for swelling and Hydrocortisone for the mineralocorticoid effect. Taper slowly post-op to avoid aseptic meningitis.

Question 49

What endocrinopathy is most common after craniopharyngioma resection?

Answer 49

DI and all are considered be Addisonian (hypoadrenal) so need steroids!

Question 50

What are the sequelae of bilateral hypothalamic injury?

Answer 50

Hyperthermia Somnolence Loss of third sensation due to damage to osmoreceptors Hyperphagia

Question 51

What do all posterior pituitary and infundibular tumours express?

Answer 51

TTF-1 (Thyroid transcription factor-1)

Question 52

What are the most common primary tumour of the infundibulum?

Answer 52

Granular cell tumours (WHO grade 1)

Question 53

What is a pituicytoma?

Answer 53

A low grade glial cell tumour of the infundibulum (WHO grade 1)

Question 54

What is a spindle cell oncocytoma?

Answer 54

Non-neuroendocrine tumour of the pituitary gland occuring in adults

Question 55

What tumours primarily arise from the neurohypophysis / infundibulum?

Answer 55

Craniopharyngioma Granular cell tumours Pituicytomas Spindle cell oncocytomas

Question 56

How would you investigate a patient with lymphoma?

Answer 56

HIV test/CD4 count CT CAP or whole body PET LP for cytology Bone marrow biopsy testicular US in males ophthalmological examination for uveitis and intraocular lymphoma

Question 57

What are the differences in imaging of lymphoma between AIDS -ve and +ve patients

Answer 57

AIDS +ve patients with lymphoma often multifocal and ring enhancing because of necrotic centre AIDS-ve lymphoma enhance homogeneously

Question 58

What are the indications for operating on lymphoma?

Answer 58

Biopsy

Question 59

Main chemotherapy agent used in treatment of lymphoma

Answer 59

Methotrexate