Genetic Tumor Syndromes Involving CNS

Question 1

The gene locus for von Recklinhausen’s disease is on which chromosome?
● A. 17
● B. 22
● C. 25
● D. 19
● E. Chromosome X

Answer 1

A. 17

Question 2

A patient presented with six café au lait spots, each ≥ 15 mm in greatest diameter along with two painful neurofibromas. Lisch nodules in NF1 are present in which of the following?
● A. Nail bed
● B. Scalp hair
● C. Iris
● D. Proximal convoluted renal tubules
● E. Lips

Answer 2

C. Iris

Question 3

A patient presented with bilateral hearing loss and seizures. Bilateral vestibular schwannomas and multiple meningiomas are hallmark of which of the following?
● A. NF1
● B. NF2
● C. Tuberous sclerosis
● D. Sturge Weber syndrome
● E. Neurocutaneous melanosis

Answer 3

B. NF2

Question 4

Which of the following is a diagnostic criterion of schwannomatosis?
● A. Germline pathogenic NF2 mutation
● B. First-degree relative with NF2 mutation
● C. Pathologically proven meningioma and germline SMARCB1 pathogenic mutation
● D. Schwannomas in previous field of radiation therapy
● E. > 1 pathologically proven schwannoma/meningioma and LOH chromosome 22

Answer 4

C. Pathologically proven meningioma and germline SMARCB1 pathogenic mutation

Question 5

Which of the following is true regarding schwannomatosis versus NF2?
● A. Most NF2 patients have chronic pain
● B. Life expectancy of schwannomatosis is worse than NF2
● C. Surgery may occasionally be associated with worsening of global pain
● D. Pain is localized and associated with the mass

Answer 5

C. Surgery may occasionally be associated with worsening of global pain

Question 6

Subependymal giant cell astrocytoma (SEGA) is associated with tuberous sclerosis (TSC). What is the most common location of SEGA in TSC?
● A. Posterior fossa
● B. Frontal lobe
● C. Sphenoid wing
● D. Foramen of Monro
● E. Torcular Herophili

Answer 6

D. Foramen of Monro

Question 7

Which of the following is not a major diagnostic criterion for tuberous sclerosis (TSC)?
● A. > 3 hypomelanocytic macules > 5 mm diameter
● B. > 3 angiofibromas
● C. > 2 ungual fibroma
● D. > 4 pits in dental enamel
● E. > 2 angiomyolipomas

Answer 7

D. > 4 pits in dental enamel

Question 8

Intracerebral calcifications are most frequently associated with which of the following?
● A. NF1
● B. NF2
● C. Tuberous sclerosis
● D. Neurocutaneous melanosis
● E. Von Ricklinghausen’s disease

Answer 8

C. Tuberous sclerosis

Question 9

Infantile myoclonus in tuberous sclerosis respond well to which of the following?
● A. Chemotherapy
● B. Radiotherapy
● C. Mannitol
● D. Steroids
● E. Hormone replacement therapy

Answer 9

D. Steroids

Question 10

According to diagnostic criteria, von Hippel-Lindau (VHL) should be suspected in an individual who has all of the following, except?
● A. Retinal angioma at a young age
● B. Spinal or cerebellar hemangioblastoma
● C. Adrenal or extra-adrenal pheochromocytoma
● D. RCC if the individual is > 47 years old
● E. Endolymphatic sac tumors

Answer 10

D. RCC if the individual is > 47 years old

Question 11

For a patient with or at risk of von Hippel-Lindau (VHL) what is the recommended guideline for retinal examination at 16 + years?
● A. Every 3 months
● B. Every 6 months
● C. Annually
● D. Every 5 years
● E. Every 10 years

Answer 11

B. Every 6 months

Question 12

A patient presented with right hemiparesis, hemiatrophy, and homonymous hemianopia along with left port-wine facial nevus. What is the most probable diagnosis?
● A. NF1
● B. NF2
● C. Tuberous sclerosis
● D. Sturge Weber syndrome
● E. Neurocutaneous melanosis

Answer 12

D. Sturge Weber syndrome

Question 13

Neuroectodermal defect during morphogenesis involving melanoblasts of skin and pia mater originating from neural crest cells leads to which of the following?
● A. NF1
● B. NF2
● C. Tuberous sclerosis
● D. Sturge Weber syndrome
● E. Neurocutaneous melanosis

Answer 13

E. Neurocutaneous melanosis

Question 14

Which of the following is an autosomal dominant syndrome with benign colonic polyposis, colorectal carcinomas, and tumors of brain with medulloblastoma being the mostly associated brain tumor?
● A. Neurocutaneous melanosis
● B. Brain tumor polyposis syndrome 1
● C. Brain tumor polyposis syndrome 2
● D. Turcot syndrome
● E. Li Fraumeni’s syndrome

Answer 14

C. Brain tumor polyposis syndrome 2

Question 15

Li Fraumeni’s syndrome is caused by germ line mutations in which of the following?
● A. TP 53
● B. 17q
● C. 19p
● D. Chromosome X
● E. 22

Answer 15

A. TP 53

Question 16

An 8-year-old patient presents in neurosurgical OPD with greater than or equal to six café au lait spots (hyperpigmented oval light brown skin macules which are present in greater than 99% cases of NF1), each greater than or equal to 5 mm in greatest dimension on his/her body, greater than or equal to
two neurofibromas, and freckling (hyperpigmentation) in the axillary or intertriginous (inguinal) areas. You diagnosed this case as NF1 or Von Recklinghausen’s disease. What other abnormalities can lead to diagnosis of this disease?
● A. Optic pathway glioma/pilocytic astrocytoma
● B. More than or equal to two Lisch nodules which are pigmented iris hamartomas that appear as translucent yellow/brown elevations that tend to become more numerous with age
● C. Distinctive osseous abnormalities like sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis
● D. A first-degree relative (parent, sibling, or offspring) with NF1 by above criteria
● E. All of the above

Answer 16

E. All of the above

Question 17

A patient presents to your OPD as diagnosed case of NF1 with optic nerve gliomas. Focal, resectable, and symptomatic lesions should be surgically removed. MEK inhibitors are approved for use in 2 to 18 years of age for symptomatic, inoperable plexiform neurofibromas. How is the patient counselled
regarding management of optic nerve gliomas?
● A. Unlike optic gliomas in the absence of NF1, these are rarely chiasmal, are often multiple, and hence have a better prognosis
● B. Most are nonprogressive and should be followed ophthalmologically and with serial imaging (MRI or CT)
● C. Surgical intervention probably does not alter visual impairment
● D. Surgery is reserved for special situations like large disfiguring tumor or pressure on adjacent structures
● E. All of the above

Answer 17

E. All of the above

Question 18

A patient presents with seizures, multiple intradural spinal tumors, retinal hamartomas, and increased antigenic nerve growth factor. He/she is diagnosed as neurofibromatosis type 2 (NF2) which is also called as MISME syndrome (multiple inherited schwannomas, meningiomas, and ependymomas). All of the following are essential diagnostic criteria of NF2 except?
● A. Unilateral vestibular schwannoma and more than two plexiform neurofibromas
● B. Bilateral vestibular schwannomas on MRI or CT of brain
● C. A first-degree relative (sibling, parent, or offspring) with NF2 and unilateral vestibular schwannomas or any two of meningioma, schwannoma, glioma, or posterior subcapsular
opacity
● D. Unilateral vestibular schwannoma and any two of meningioma, schwannoma, glioma, or posterior subcapsular opacity
● E. Multiple meningiomas and unilateral vestibular schwannoma or any two of ependymoma, schwannoma, or posterior subcapsular opacities

Answer 18

A. Unilateral vestibular schwannoma and more than two plexiform neurofibromas

Question 19

A patient presents with bilateral vestibular schwannomas with intact hearing in both ears. Surgery is planned and MRI of cervical spine is done prior to surgery to rule out any intraspinal tumor. Which statement regarding surgical treatment of
this patient is not true?
● A. Smaller tumor is removed first and if hearing is serviceable in the operated side, then the other tumor should be operated
● B. If hearing is not preserved in the operated side, then the other tumor is followed with serial imaging as long as possible
● C. If there is need to operate on the second VS after failure to preserve hearing in the first VS surgery, then subtotal resection is done
● D. If bilateral VS are present and both are asymptomatic then there is no need to operate
● E. Stereotactic radiosurgery is an alternative treatment option

Answer 19

D. If bilateral VS are present and both are asymptomatic then there is no need to operate

Question 20

Schwannomatosis typically presents with multiple schwannomas (spinal, cutaneous or cranial) and less frequently with meningiomas (cranial and spinal) with a propensity for spinal and paraspinal nerves and less frequently for meninges. What is the essential criterion for schwannomatosis?
● A. More than or equal to two schwannomas (nonintradermal and pathologically confirmed) and no bilateral VS on highquality MRI
● B. One schwannoma or meningioma and one affected first degree relative
● C. Germline SMAECB1 and LZTR1 mutations
● D. Loss of heterozygosity/deletion of chromosome 22 and two different NF2 mutations
● E. Both A and B

Answer 20

E. Both A and B

Question 21

Schwannomatosis (SWN) presents with chronic pain and pain associated with mass. MRI of entire neuraxis and molecular genetic testing of the biopsied mass should be done. Which statement regarding treatment of SWN is correct?
● A. Surgery should be done for asymptomatic lesions as these can progress to malignant tumor
● B. Surgery for symptomatic schwannomas may relieve local pain
● C. Medical therapy with methotrexate is recommended
● D. There is no chance of worsening of global pain after surgery
● E. Life expectancy is reduced in these patients

Answer 21

B. Surgery for symptomatic schwannomas may relieve local pain

Question 22

A patient presents with history of myoclonus which converted to generalized tonic clonic seizure. This patient also has facial adenomas which are present since childhood. CT of brain shows intracerebral calcifications primarily located in subependymal region in the walls of lateral ventricles, and these protrude into ventricles causing candle guttering. Treatment of this disease is observation, with surgery (transcallosal or ventriculoscopic approach) reserved for symptomatic lesions like subependymal giant cell astrocytoma (SEGA). What is a major criterion for diagnosis of this condition (tuberous sclerosis complex)?
● A. More than or equal to three hypomelanotic macules more than or equal to 5 mm diameter
● B. More than or equal to three angiofibromas or fibrous cephalic plaque
● C. More than or equal to two ungual fibroma
● D. Shagreen patch
● E. All of the above

Answer 22

E. All of the above

Question 23

A 60-year-old patient presents to your OPD as diagnosed case of hemangioblastoma of cerebellum, renal cell carcinoma, and pheochromocytoma. Other tumors that are associated with this condition are endolymphatic sac tumors, pancreatic neuroendocrine tumors and cysts, broad ligament cystadenomas, and epididymal cystadenomas. Treatment options for this condition include belzutifan, surgical resection of symptomatic lesion, or stereotactic radiosurgery. What subtype von Hippel-Lindau (VHL) disease is this?
● A. Type 1
● B. Type 2A
● C. Type 2B
● D. Type C
● E. Type D

Answer 23

C. Type 2B

Question 24

Li Fraumeni’s syndrome is associated with CNS tumors like primarily SHH activated medulloblastomas, IDH wild-type high-grade gliomas, and choroid plexus carcinomas. Essential
criterion for this condition is pathogenic germline alteration in the TP 53 gene. What is the classic criterion for diagnosis of this disease?
● A. Sarcoma before the age of 45 years
● B. A first-degree relative with any cancer before the age of 45 years
● C. A first- or second-degree relative with any cancer before the age of 45 years, sarcoma at any age
● D. All of the above
● E. A first-degree relative with cancer after the age of 55 years with sarcoma as well

Answer 24

D. All of the above

Question 25

A patient presents with history of seizures, left-sided body weakness, right-sided facial port-wine nevus in the distribution of 1st division of trigeminal nerve, and growth hormone deficiency. On investigations, this patient shows curvilinear double parallel lines or tram tracking on plain skull X-rays, increased intraocular pressure, and leptomeningeal angiomatosis. What is the most probable diagnosis in this case?
● A. Sturge-Weber syndrome
● B. Tuberous sclerosis
● C. Turcot syndrome
● D. Cowden syndrome
● E. Carney syndrome

Answer 25

A. Sturge-Weber syndrome