Neurofibromatosis

1. N A M E : K . S R I M AT H I - C R M I
B AT C H : 2 0 1 7
T O P I C : N E U R O F I B R O M AT O S I S

2. N E U R O F I B R O M A T O S I S – T Y P E 1
About:
 First described by ‘Frederich von reclinghausen’ in 1882.
 NF1 is an inherited disorder that affects about one in 2500 to one in 3000 people worldwide,
irrespective of sex or ethnic origin.
 Prone to develop benign and malignant tumours of the CNS and peripheral nervous system,
in addition to malignant diseases affecting other parts of the body.
 NF1 is a condition characterized by changes in skin colouring (pigmentation) and the growth
of tumours along nerves in the skin, brain, and other parts of the body.

3. F R E Q U E N C Y :
 Neurofibromatosis type 1 occurs in 1 in 3,000 to 4,000 people worldwide.
C A U S E S :
 Mutations in the NF1 gene cause neurofibromatosis type 1.
 The NF1 gene provides instructions for making a protein called neurofibromin.
 This protein is produced in many cells, including nerve cells and specialized cells surrounding
nerves
 Neurofibromin acts as a tumor suppressor, which means that it keeps cells from growing and
dividing too rapidly or in an uncontrolled way.

4. I N H E R I T A N C E :
 Neurofibromatosis type 1 is considered to have an autosomal dominant pattern of inheritance.
 People with this condition are born with one mutated copy of the NF1 gene in each cell.
 In about half of cases, the altered gene is inherited from an affected parent.
 The remaining cases result from new mutations in the NF1 gene and occur in people with no
history of the disorder in their family.

5. C O M M O N L Y A S S O C I A T E D T U M O R S :
Lifetime risk
Glioma of the optic pathway 15-20%
Other brain tumour More than fivefold increase
Malignant peripheral nerve-sheath tumour 8-13%
Gastrointestinal stromal tumour 4-25%
Breast cancer About fivefold increase
Leukaemia About sevenfold increase
Phaeochromocytoma 0-1-57%
Duodenal carcinoid tumour 1%
Rhabdomyosarcoma 14-6%

6. D I A G N O S T I C C R I T E R I A :
Two or more of the following clinical features are sufficient to establish a diagnosis of NF1.
 Six or more café-au-lait macules (>0-5 cm at largest diameter in a prepubertal child or>1-5 cm in
post-pubertal individuals).
 Axillary freckling or freckling in inguinal regions.
 Two or more neurofibromas of any type or one or more plexiform neurofibromas.
 Two or more Lisch nodules (iris hamartomas).
 A distinctive osseous lesion (sphenoid wing dysplasia, long-bone dysplasia).
 An optic pathway glioma.
 A first-degree relative with neurofibromatosis type 1 diagnosed by the above criteria.

7. G E N E T I C S :
 Germline mutation in the NF1 tumour-suppressor gene.
 Spontaneous mutation.
 Individuals with NF1 microdeletions tend to develop neurofibromas at an earlier age, have a lower
mean IQ, manifest abnormal facial features, and are at increased risk of developing malignant
peripheral nerve-sheath tumours.
 Genetic testing.

8. C L I N I C A L F E A T U R E S :
Skeletal abnormalities:
 Osteopenia.
 Scoliosis.
 Sphenoid wing dysplasia.
 Congenital tibial dysplasia.
 Pseudarthrosis.

9. Nervus system tumors:
 Optic pathways and brainstem gliomas.
 Glioblastomas.
 Malignant peripheral nerve sheath tumours (Neurofibrosarcomas or neurogenic sarcomas).

10. Non nervous system tumors:
 Gastrointestinal stromal tumours.
 Breast cancers.
 Leukaemia and lymphoma.
 Phaeochromocytoma.
 Duodenal carcinoids.
 Rhabdomyosarcomas.

11. N E U R O F I B R O M A T O S I S – T Y P E 2
About:
 Neurofibromatosis type 2 (NF2) is a genetic condition that causes tumours to grow along
your nerves.
 The tumours are usually non-cancerous (benign) but may cause a range of symptoms.

12. N F 2 S Y M P T O M S :
 Dizziness.
 Hearing loss, which may begin as early as the teenage years.
 Tinnitus (ringing in the ears)
 Problems with facial expressions.
 Issues with balance.
 Difficulty walking.

13. D I F F E R E N C E B / W N F 1 & N F 2 :
 In NF1, the tumors occur in the small nerves of the skin and the large nerves inside your body, in
NF2, tumors primarily affect the auditory nerves that connect the ears to the brain and control
hearing.
 NF2 patients can also develop tumors in the nerves of their body.
 The risk of cancer is very low in NF2, but tumors can still lead to deafness, pain, weakness and/or
numbness.
 People with NF2 are also at risk of other tumors arising from the tissue wrapping around the brain
and spinal cord (meningiomas), and tumors occurring in the deep fluid filled spaces of the brain and
spinal cord.

14. C A U S E S O F N F 2 :
 Neurofibromatosis type 2 (NF2) is caused by a faulty gene. If the NF2 gene is faulty, it leads to
uncontrolled growths (tumours) developing in the nervous system.
 In half of all cases of NF2, the faulty gene is passed from a parent to their child. Only 1 parent
needs to have the faulty gene for their child to be at risk of developing the condition.
 If either the mother or father has the faulty gene, there's a 1 in 2 chance that each child they have
will develop NF2.

15. D I A G N O S I S O F N F 2 :
 Bilateral (meaning both sides) vestibular schwannomas, which are tumors that grow from the nerve
that controls hearing and balance.
 A parent, sibling, or child with NF2 and either of the following:
A single vestibular schwannoma diagnosed before age 30.
Any 2 of the following: a meningioma, glioma, schwannoma, or cataract.
 A single vestibular schwannoma diagnosed before age 30 and a meningioma, glioma, schwannoma,
or cataract.
 Multiple meningiomas and a unilateral meaning affecting only 1 side vestibular schwannoma
diagnosed under age 30, a glioma, schwannoma, or cataract

16. G A S T R O I N T E S T I N A L S T R O M A L T U M O R
About:
 A gastrointestinal stromal tumor (GIST) is a type of cancer that begins in the digestive
system.
 GIST’s happen most often in the stomach and small intestine.
 A GIST is a growth of cells that's thought to form from a special type of nerve cells.
 These special nerve cells are in the walls of the digestive organs.
 They play a part in the process that moves food through the body.

17. S Y M P T O M S :
Small GISTs may cause no symptoms, and they may grow so slowly that they don't cause problems at first.
As a GIST grows, it can cause signs and symptoms. They might include:
 Abdominal pain
 A growth you can feel in your abdomen
 Fatigue
 Nausea
 Vomiting
 Cramping pain in the abdomen after eating
 Not feeling hungry when you would expect to
 Feeling full if you eat only a small amount of food
 Dark-colored stools caused by bleeding in the digestive system.

18. P R E V E N T I O N :
 The only known risk factors for gastrointestinal stromal tumors (GISTs) − older age and
certain rare, inherited genetic syndromes – cannot be changed.
 There are no known lifestyle-related or environmental causes of GISTs, so at this time we do
not know of any way to protect against these cancers.

19. D I A G N O S I S :
 Catching cancer early often allows for more treatment options.
 Some early cancers may have signs and symptoms that can be noticed, but that is not always
the case.

20. T R E A T M E N T S :
 Surgery for Gastrointestinal Stromal Tumors.
 Targeted Drug Therapy for Gastrointestinal Stromal Tumors.
 Ablation and Embolization to Treat Gastrointestinal Stromal Tumors.
 Chemotherapy for Gastrointestinal Stromal Tumors.
 Radiation Therapy for Gastrointestinal Stromal Tumors

21. C L I N I C A L M A N I F E S T A T I O N S :
 Mesenchymal tumors of the GI tract are often asymptomatic and discovered incidentally
during endoscopic or barium studies.
 Overt GI bleeding — 40 percent
 Abdominal mass — 40 percent
 Abdominal pain —- 20 percent
 The vast majority of GIST metastases at presentation are intra-abdominal, either with
metastases to the liver, omentum, or peritoneal cavity.

22. I M A T I N I B ( G L E E V E C ) A T Y R O S I N E - K I N A S E
I N H I B I T O R :
 Imatinib (Gleevec) is very effective for CD114 positive GISTs
 It also has antitumor effficacy in tumors that lack KIT mutations but have alterations in the
PDGF pathway
 Some PDGFRa mutations are imatinib- sensitive, others not therefore, patients with advanced
tumors that are histologically c/w GIST should not be denied a trial of imatinib if they are c-kit
negative.

23. T H E I N C I D E N T A L U C S U B E P I T H E L I A L M A S S :
 No firm clinical guidelines or consensus
 Surface Endoscopy can establish a lipomatous nature of the mass
 If mass is > 1 cm referral for EUS, if < 1 cm repeat EGD in one year, if stable probably no
follow-up
 If mass arises from muscle layer (4th EUS layer mass) and is > 3 cm referral for surgery
(likely GIST)
 Clinical conundrum: The 1 - 3 cm mass
 4th layer mass should undergo EUS-FNA and c-kit staining
 If a GIST is found discuss management strategies, esp.

24. THANK YOU