path genetic and paediatric disease - formatted

Question 1

1. 56.APRIL02 A 38-year-old prostitute suicides after finding she is 5 months pregnant. Autopsy shows tertiary syphilis. Changes of this are most likely to be seen in
2. The maternal central nervous system
3. The maternal heart and aorta
4. The maternal genital tract
5. The maternal skull, facial bones and molar teeth
6. The fetus

Answer 1

2. The maternal heart and aorta (80% to 85%)

• Tertiary syphilis occurs years after the initial infection
o most frequently involves the aorta (80% to 85%);
o the central nervous system (5% to 10%);
o liver, bones, and testes (gummas).
• Aortitis is manifested by aortic aneurysms in which there is inflammatory scarring of the tunica media, widening and incompetence of the aortic valve ring, and narrowing of the mouths of the coronary ostia
• Neurosyphilis takes one of several forms, designated meningovascular syphilis, tabes dorsalis, and general paresis
• Syphilitic gummas are white-gray and rubbery, occur singly or multiply, and vary in size from microscopic defects resembling tubercles to large tumor-like masses.
o They occur in most organs but particularly in skin, subcutaneous tissue, bone, and joints.
o In the liver, scarring as a result of gummas may cause a distinctive hepatic lesion known as hepar lobatum
• On histologic examination, the gummas contain a center of coagulated, necrotic material and margins composed of plump or palisaded macrophages and fibroblasts surrounded by large numbers of mononuclear leukocytes, chiefly plasma cells.
• Treponemes are scant in these gummas and are difficult to demonstrate

• Paretic neurosyphilis - gradual loss of mental and physical function with mood alteration progressing to dementia, Argyll Robertson pupil (prostitutes pupil - accommodates but doesn’t react)

 

Question 2

2. 38.APRIL02 3-year-old girl has an 11 cm left flank neoplasm stretching across the epigastrium to within 1 cm of the right kidney. There are no nodes or other disease. In many areas it cannot be separated from left kidney, adrenal or retroperitoneal muscle. Urinary VMA [vanillylmandelic acid] levels are elevated. What is her likely prognosis, with treatment?
3. 95 -100% Cure
4. 85 to 98% 5-year survival
5. 50 – 70 % 5-year survival
6. 5 – 15 % 5-year survival
7. Less than 3% 1-year survival

Answer 2

3. 50 – 70 % 5-year survival - T - Among patients with stage 3 NB outcome varies according to age at diagnosis and histologic features: in one study, four-year event free survival was 93% for infants, but only 54% for patients older than 2y of age with unfavorable biologic features.
4. 38.APRIL02 3-year-old girl has an 11 cm left flank neoplasm stretching across the epigastrium to within 1 cm of the right kidney. There are no nodes or other disease. In many areas it cannot be separated from left kidney, adrenal or retroperitoneal muscle. Urinary VMA [vanillylmandelic acid] levels are elevated. What is her likely prognosis, with treatment? Rob p 253 - stage III with no dissemination (TW) (–)
5. 95 -100% Cure
6. 85 to 98% 5-year survival
7. 50 – 70 % 5-year survival - T - Among patients with stage 3 NB outcome varies according to age at diagnosis and histologic features: in one study, four-year event free survival was 93% for infants, but only 54% for patients older than 2y of age with unfavorable biologic features.
8. 5 - 15 % 5-year survival - this was previously considered the correct option. Donnelly says stage III (ie tumor extension crossing midline) prognosis is 30% survival.
9. Less than 3% 1-year survival
   Neuroblastoma
   • Increased urinary VMA, HVA (80-90%)
   • Low risk-tumors (stage 1 or 2 disease, infants with stage 4S and favorable biologic factors): surgery is primary treatment. 2yr event-free survival is 85-100%.
   • Intermediate- or high-risk (stage 3 neuroblastoma) 54% for patients older than 2yo, and 93% for infants.
   • >1year - Stages III and IV only 10% 5YS despite treatment
   • Age and stage are important determinants of outcome
   • Infants younger than 1 year of age have an excellent prognosis regardless of the stage of the neoplasm
   o Most often in this age group, the neoplasms are stage I or II
   o At this early age, even when metastases are present, in about half the spread is limited to the liver, bone marrow, and skin (stage IV-S), and such infants have at least an 80% 5-year survival with only minimal therapy
   o Even when the dissemination is more widespread in the first year of life, the survival is greater than 50%
   o At this age with stages I or II, therapy yields a 95 to 98% survival
   • Children older than 1 year of age with stages III and IV tumor have only a 10% survival despite all forms of treatment

 

Question 3

4. 36.APRIL02 You are performing an ultrasound on a 20-year-old woman for upper abdominal pain. Her request form says only “Gaucher Disease”. She has an enlarged liver and spleen with moderate generalised lymphadenopathy. The best explanation for this is?
5. They are expected findings in Gaucher Disease
6. Liver disease with portal hypertension
7. Associated acute leukaemia
8. Cardiomyopathy with right heart failure
9. Incorrect information; most patients with Gaucher Disease die in early childhood

Answer 3

1. They are expected findings in Gaucher Disease

• Gaucher disease is an inborn error of metabolism that affects the recycling of cellular glycolipids.
• Autosomal recessive, deficiency of glucocerebrosidase. Get accumulation of glucocerebroside and other glycolipids within the lysosomes of macrophages (“Gaucher Cells”). Get accumulation of these lipid-laden macrophages in spleen, liver, bone marrow, and bone. Have associated inflammatory response. Can be treated by replacement of the deficient enzyme.
• GD classically categorized into 3 clinical types.
• Type I, 90%, nonneuronopathic form.
o In this type, storage of glucocerebrosides is limited to the mononuclear phagocytes throughout the body without involving the brain.
o Splenic and skeletal involvements dominate this pattern of the disease.
o It is found principally in Jews of European stock.
o Patients with this disorder have reduced but detectable levels of glucocerebrosidase activity.
o Longevity is shortened but not markedly.
• Type II, or acute neuronopathic, Gaucher disease is the infantile acute cerebral pattern.
o This infantile form has no predilection for Jews.
o In these patients, there is virtually no detectable glucocerebrosidase activity in the tissues.
o Hepatosplenomegaly is also seen in this form of Gaucher disease, but the clinical picture is dominated by progressive central nervous system involvement, leading to death at an early age.
• Type III, subacute or chronic neuronopathic form.
o These patients are usually juveniles and have the systemic involvement characteristic of type I but have progressive central nervous system disease that usually begins in the teens or twenties.
o These specific patterns run within families, resulting from different allelic mutations in the structural gene for the enzyme.
• In types II and III, central nervous system dysfunction, convulsions, and progressive mental deterioration dominate, although organs such as the liver, spleen, and lymph nodes are also affected.

Question 4

3. 37.APRIL02 A 12-year-old boy has a right retroperitoneal fibrosarcoma. His mother says that at 2 years of age he had a cancer of the right kidney and over next 10 years developed a progressive severe scoliosis, convex to the left. Which of the following is most accurate in regards to the history provided;
4. Past Wilms’ tumour associated with neurofibromatosis Type 1
5. Past Wilms’ tumour associated neurofibromatosis Type II
6. Past Wilms’ tumour associated with complications of treatment
7. Past Wilms’ tumour associated with WAGR syndrome
8. Past mesoblastic nephroma with malignant degeneration

Answer 4

3. Past Wilms’ tumour associated with complications of treatment – however this would depend on the stage of the tumor: ie stage I and II Sx and chemo, stage III and IV – add XRT. Some groups use XRT for stage II. Cx resulting from radiotherapy include muscle atrophy, short stature, and scoliosis.
4. 37.APRIL02 A 12-year-old boy has a right retroperitoneal fibrosarcoma. His mother says that at 2 years of age he had a cancer of the right kidney and over next 10 years developed a progressive severe scoliosis, convex to the left. Which of the following is most accurate in regards to the history provided; Rob p 253 (–) (TW)
5. Past Wilms’ tumour associated with neurofibromatosis Type 1
6. Past Wilms’ tumour associated neurofibromatosis Type II
7. Past Wilms’ tumour associated with complications of treatment – however this would depend on the stage of the tumor: ie stage I and II Sx and chemo, stage III and IV – add XRT. Some groups use XRT for stage II. Cx resulting from radiotherapy include muscle atrophy, short stature, and scoliosis.
8. Past Wilms’ tumour associated with WAGR syndrome – F – Wilms tumor, aniridia, genitourinary anomalies, mental retardation.
9. Past mesoblastic nephroma with malignant degeneration
   • Radiation induces scoliosis concave to side of treatment as it causes reduced growth on that side
   o Therefore right wilms tumour with radiotherapy causes a levoconvex scoliosis (left convex)
   • Patients with NF have 10% risk of developing fibrosarcoma
   • Association between NF 1 and Wilms
   • Patients with neurofibromatosis-1 have a twofold to fourfold greater risk of developing other tumors, especially Wilms’ tumors, rhabdomyosarcomas, meningiomas, optic gliomas, and pheochromocytomas.
   • Affected children are at increased risk of developing chronic myeloid leukemia.

Question 5

5. 35.APRIL02 A couple attend for an obstetric scan at 37 weeks. The wife is concerned, as she was exposed to rubella at 7 weeks. Blood samples confirmed seroconversion at that time but they declined any further counselling. Which of the following is the most correct statement?
6. There is “no risk” (less than 0.01%) of tetatogenesis from infection at 7 weeks.
7. There is minimal (< 2%) risk of congenital abnormality, as “successful” infection at seven weeks usually causes abortion
8. There is a 5% chance of cataract, deafness or cardiac defect
9. There is a 20% chance of cataract, deafness or cardiac defect
10. There is a 70% chance of cataract, deafness or cardiac defect

Answer 5

4. There is a 20% chance of cataract, deafness or cardiac defect - T
5. 35.APRIL02 A couple attend for an obstetric scan at 37 weeks. The wife is concerned, as she was exposed to rubella at 7 weeks. Blood samples confirmed seroconversion at that time but they declined any further counselling. Which of the following is the most correct statement? Rob p 251 (TW)
6. There is “no risk” (less than 0.01%) of tetatogenesis from infection at 7 weeks – F 81% of 1st TM infection rate. Risk of congenital defects is in first 16wks of pregnancy, and minimal risk after 20wks.
7. There is minimal (< 2%) risk of congenital abnormality, as “successful” infection at seven weeks usually causes abortion – F – 81% infection rate 1st TM.
8. There is a 5% chance of cataract, deafness or cardiac defect – F – 10-25%
9. There is a 20% chance of cataract, deafness or cardiac defect - T
10. There is a 70% chance of cataract, deafness or cardiac defect
    • Maternal-fetal transmission occurs via hematogenous spread and varies with gestational age. Virus probably spreads through vascular system of developing fetus after infecting the placenta.
    • In the first TM, fetal infection rates up to 81%, dropping to 25% in 2nd TM, then increasing to 35% at 27-30 weeks, to nearly 100% for fetuses exposed beyond 36wks.
    • However, risk of congenital defects after maternal infection is essentially limited to maternal infection in the first 16 weeks of pregnancy. Little, if any, risk of congenital rubella syndrome is associated with infection after 20wks gestation.
    • Congenital Rubella Syndrome is the presence of any of the follow defects or laboratory data, or a persistently elevated IgG titer that fails to drop 2-fold per month.
    o Audiologic defects, predominantly sensorineural deafness (60-75%)
    o Ophthalmologic abnormalities (10-25%) particularly cataracts, pigmentary and congenital glaucoma.
    o Cardiac malformations (10-20%) such as PDA or peripheral pulmonary artery stenosis
    o Neurologic sequelae (10-25%) ranging from meningioencephalitis to behaviour disorders and mental retardation.

Question 6

6. 7.03.13 Child with mass FNA shows small round blue cells – LEAST LIKELY diagnosis is ?
7. Neuroblatoma
8. Ewings
9. Rhadomyosarcoma
10. Wilms
11. Retinoblastoma

Answer 6

4. Wilms tumour - F - classic Wilms tumor comprised of 3 cell types - Blastemal cells (undifferentiated cells), Stromal cells (immature spindle cells and heterologous skeletal, cartilage, osteoid, or fat), and epithelial cells (Glomeruli and tubules).
5. 7.03.13 Child with mass FNA shows small round blue cells – LEAST LIKELY diagnosis is ? (TW)
6. Neuroblastoma - T - small, primitive-appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders growing in solid sheets.
7. Ewing’s sarcoma - T - monotonous sheets of small round blue cells with hyperchromatic nuclei and scant cytoplasm.
8. Rhabdomyosarcoma - T - subtypes Botryoid and spindle cell (leiomyomatous / Embryonal / Alveolar / Undifferentiated. Histo of embryonal and alveolar types - cells have scant cytoplasm and a centrally placed round nucleus that occupies the majority of the cell.
9. Wilms tumour - F - classic Wilms tumor comprised of 3 cell types - Blastemal cells (undifferentiated cells), Stromal cells (immature spindle cells and heterologous skeletal, cartilage, osteoid, or fat), and epithelial cells (Glomeruli and tubules).
   * LW: Wilms in globally incorporated within the list of small blue cells, but out of the above list is likely least likely.
10. Retinoblastoma - T - sheets, trabeculae and nests of small blue cells with scant cytoplasm.
    Ewing’s sarcoma family of tumors (EFT) includes Ewings sarcoma, extraosseous Ewing’s sarcoma, more differentiated neuroectodermal tumors (PNET: previously AKA neuroepithelioma, adult neuroblastoms, Askin’s tumor of chest wall).

Question 7

7. 7.03.14 Patient with cystic fibrosis – long term survival is associated with?
8. No increase risk of malignancy
9. Increase risk of malgnancy only if has transplant
10. Increase risk of GIT and lymphoma
11. Increase risk of GIT, pancreas, biliary and lymphoma
12. Increase risk of cholangiocarcinoma

Answer 7

*LW:
UTD states People with CF have an increased risk of digestive tract cancers, including cancers of the small bowel, colon, pancreas, and biliary tract. No mention of lymphoma…..

4. Increase risk of GIT, pancreas, biliary and lymphoma

• New reports suggesting an increase risk of digestive cancer – entire GIT, biliary tract,liver and pancreas
• Cancer risk in nontransplanted and transplanted cystic fibrosis patients: a 10-year study.
• We observed an increased risk of digestive tract cancers among adult CF patients, particularly of the small bowel, colon, and biliary tract.
o This increased risk appeared to be more pronounced in patients who had had an organ transplantation

Question 8

8. 7.03.27 Short female patient with webbed neck and previous coarctation repair presents for thyroid ultrasound, MOST LIKELY diagnosis?
9. Turners with thyroid adenoma
10. Turners with Hashimotos
11. Familial medullary carcinoma
12. Men II
13. Achondraplasia

Answer 8

2. Turners with Hashimotos

Turners
• Autoantibodies to thyroid in 50%  hypothyroidism in 50% of these
• Approximately 1/3 of individuals with Turner syndrome have a thyroid disorder, usually hypothyroidism.
• Symptoms of this condition include decreased energy, dry skin, cold-intolerance and poor growth.
• In most cases, it is caused by an immune system attack on the thyroid gland (also known as Hashimoto’s thyroiditis).
• Although it is not known why thyroid disorders occur with a high frequency in Turner syndrome, the condition is easily treated with thyroid hormone supplements.

Question 9

9. 7.03.28 In Trisomy 21 which is TRUE ?
10. 0.5% are mosiacs/ translocations
11. 5% have associated CHD
12. live < 30 years
13. if live > 40 years 80% have Alzeimer type neurogerative disorder
14. increased risk of CML

Answer 9

4. if live > 40 years 80% have Alzeimer type neurogerative disorder – T – adults with DS usually develop neuropathologic and functional changes typical of Alzheimer disease by the 5th decade of life. One report shoe 50% of DS individuals over 35y had dementia.
5. 7.03.28 In Trisomy 21 which is TRUE ? (TW)
6. 0.5% are mosiacs/ translocations – F - Robertsonian translocation-3- 4% + Mosaics- 2-3% = 5%
   *LW: translocation = 4%, mosaic = 1%
7. 5% have associated CHD – F – approximately 50% of individuals with DS have congenital heart disease.
8. live < 30 years – F – life expectancy 58.6yo. Majority live past 30yo.
9. if live > 40 years 80% have Alzeimer type neurogerative disorder – T – adults with DS usually develop neuropathologic and functional changes typical of Alzheimer disease by the 5th decade of life. One report shoe 50% of DS individuals over 35y had dementia.
10. increased risk of CML – F - transient leukemia (newborns with DS) 20%. Acute megakaryoblastic leukemia (AMKL) 1 in 50-200 with DS, about 500x increased risk. Acute lymphoblastic leukemia (ALL) 10-20x increased risk.
    • Meiotic non-disjunction in ovum
    • 47 chromosomes (extra chromosome maternal in 95%)
    • Parents = normal karyotype
    • Alzheimer’s disease
    o Develops in virtually all >40 yrs
    o Abnormal immune responses
    • CHD
    o 40%
    o Endocardial cushion- most common
    o Ostium primum, ASD, AV valve defects, VSD
    o Responsible for majority of deaths in infancy and childhood
    • Blokes with DS tend to shoot blanks. Chicks with DS can get knocked up, but have increased chance of sharing that extra chromosome (in one series 30 pregnancies in 26 women resulted in 10 offspring with DS, 18 without, and 3 spontaneous abortions).

Question 10

10. 7.03.97 Second Retinoblastoma Tumour – other sites to image include ?
11. pineal
12. cavernous sinus
13. cranial vault/sutures
14. pineal or suprasellar region

Answer 10

4. pineal or suprasellar region – T - May also have third or fourth independently arising tumour in pineal or suprasellar region (trilateral or quadrilateral retinoblastoma)

RB = rare malignant congenital intraocular tumor arising from the primitive photoreceptor cells of retina.
Flexner-Wintersteiner rosettes (in 50%) = neuronal cells line up around an empty centra zone filled with polysaccharides = very specific for retinoblastomas.
About 50% of all childhood leukokoria are caused by RB.

Question 11

11. 02.19 A 6year old child has large mass involving adrenal gland/kidney and one ipsilateral lymph node, urine is positive for VMA. What is the staging?
12. Stage I
13. Stage II
14. Level 2
15. Stage II S
16. Level 3

Answer 11

2. Stage II – T – stage I or 2B depending on whether ipsilateral node was adherent (ie node attached to and removed with primary tumor) or non-adherent to tumor. See below.

International neuroblastoma staging system (revised in 1993) UTD 2009.
• Stage 1: localized tumor with complete gross excision, +/- microscopic residual disease; negative ipsilateral nodes (nodes attached to and removed with primary tumor may be positive)
• Stage 2A: localized tumor with incomplete gross excision; negative ipsilateral nodes.
• Stage 2B: localized tumor with incomplete gross excision; positive ipsilateral nodes; negative contralateral nodes.
• Stage 3: Unresectable unilateral tumor infiltrating across midline, +/- regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration or by lymph node involvement.
• Stage 4: Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin and/or other organs (except as defined for 4S)
• Stage 4S: Localised primary tumor (as defined for stage 1, 2A, or 2B), with dissemination limited to skin, liver, and/or bone marrow (limited to infants <1y age).
• (–)In general, based on many of the aforementioned factors, neuroblastomas can be classified into three groups
1. The first group is characterized by a hyperdiploid or near-triploid content of DNA and high levels of Trk A expression in the absence of N- myc amplification and chromosome 1p deletions. These tumors tend to occur in infants with low stage (I, II, or IV-S) disease, and the cure rate is greater than 90%.
2. The second group is characterized by a near-diploid or tetraploid DNA content, absence of N- myc amplification, frequent chromosome 1p deletions, and usually low levels of Trk A expression. These tumors tend to occur in older patients with more advanced stage (III or IV) and are slowly progressive with a cure rate of 25 to 50%.
3. The third and final group of neuroblastomas has multiple unfavorable features and is associated with the worst prognosis and a cure rate of less than 5%. These neuroblastomas tend to occur in children between 1 and 5 years of age with advanced stage disease and are characterized by N- myc amplification, usually in the presence of a diploid or tetraploid DNA content, chromosome 1p deletions, and minimal Trk A expression.

Question 12

12. Sep03.06 Fragile X which is FALSE?
13. mental retardation
14. mandible large
15. hyperextensible lax joints
16. macro-orchidism (90%)

Answer 12

12. Sep03.06 Fragile X which is FALSE? (TW)
13. mental retardation – T – most common inherited cause of mental retardation.
14. mandible large - T - long face with a large mandible (Robbins). Jaw is usually large in adulthood patients with FXS.
15. hyperextensible lax joints - T - hyperextensible joints (Robbins). hyperflexible joints occasionally occur (UTD). Most common MSK manifestation in FXS include flexibl pes planus (flat feet), excessive joint laxity, and scoliosis. LW of options provided this would be least correct, but i fovor an incomplete recall of the correct false answer
16. macro-orchidism – T – most postpubertal males develop macroorchidism.
    • Most common inherited cause of mental retardation (UTD) where as Robbins says it’s the second most common after Down syndrome. X linked disorder caused by expansion of a repetition of the cytosine-guanine-guanine trinucleotide segment (CGG) of the fragile X mental retardation 1 (FMR-1) gene.

Question 13

13. Sep03.41Retinoblastoma, which is the least likely ?
14. Very radio sensitive. Excellent prognosis even if it extends retro-orbitally
15. Carriers of RB gene have a 90% risk
16. Can get extraocular Retinoblastomas

Answer 13

1. Very radio sensitive. Excellent prognosis even if it extends retro-orbitally - F - enuleation usually is indicated for large tumors with no visual potential, blind, painful eyes, and/or tumors that extend into the optic nerve. External beam XRT was original globe-sparing treatment for Rb. Risk of tumor recurrence following ext XRT 7%, occurring within 40months. Also risk of secondary cancers with XRT. UpToDate.
2. Sep03.41Retinoblastoma, which is the least likely ? (TW) (–)
3. Very radio sensitive. Excellent prognosis even if it extends retro-orbitally - F - enuleation usually is indicated for large tumors with no visual potential, blind, painful eyes, and/or tumors that extend into the optic nerve. External beam XRT was original globe-sparing treatment for Rb. Risk of tumor recurrence following ext XRT 7%, occurring within 40months. Also risk of secondary cancers with XRT. UpToDate.
4. Carriers of RB gene have a 90% risk - T - If a mutant RB allele arises in the germ line, it can be transmitted as a dominant trait, and carriers are at high risk (>90% risk for most mutations) for retinoblastoma. Robbins.
5. Can get extraocular Retinoblastomas - T - trilateral RB = bilateral RB with neuroectodermal pineal tumor. Quadrilateral RB = trilateral RB with 4th focus in suprasellar cistern. Dahnert 6th.
   • The tumor is usually fatal once it spreads outside the eye and orbit.
   • If a mutant RB allele arises in the germ line, it can be transmitted as a dominant trait, and carriers are at high risk (>90% risk for most mutations) for retinoblastoma in childhood and for other cancers (e.g., osteosarcoma) later in life.
   • a small percent have, in addition, independently arising tumors, also occurring in childhood, either in the pineal gland or in the suprasellar or parasellar region (trilateral retinoblastoma).
   • Rarely, tumors composed of uniformly benign-appearing cells exhibiting photoreceptor differentiation and the formation of fleurettes have been reported. These have been referred to as retinocytomas and are believed to be a benign variant of retinoblastoma (SOh: but considered pre-malignant- Robbins pg 1339)

Question 14

14. Sep03.70 Tracheo-oesophageal fistula – most common type:
15. Proximal fistula, distal blind pouch
16. “H” type
17. Distal fistula, proximal pouch
18. Misnomer because no atresia
19. Misnomer because no fistula

Answer 14

3. Distal fistula, proximal pouch - T - oesophageal atresia and tracheo oesophageal fistula not in communication with proximal oesophagus (82%)

Question 15

1. 15 yo M solid hypothalamic lesion, most likely
2. pilocytic astrocytoma
3. GBM
4. Craniopharyngioma

Answer 15

1. pilocytic astrocytoma – T – PA is the most common pediatric CNS glial neoplasm and the most common pediatric cerebellar tumor. Cerebellum, optic nerve and chiasm, and hypothalamic region are the most common locations.
2. 15 yo M solid hypothalamic lesion, most likely (TW)
3. pilocytic astrocytoma – T – PA is the most common pediatric CNS glial neoplasm and the most common pediatric cerebellar tumor. Cerebellum, optic nerve and chiasm, and hypothalamic region are the most common locations.
4. GBM – F – too young
5. Craniopharyngioma – F – adamantinomatous type: cystic lesion in this age group (in adults, squamous-papillary type can be solid).
   Pilocytic astrocytomas: most cases manifest in the first 2 decades of life. Most lesions occur in or near the midline, usually arising from the cerebellum, optic nerve and chiasm, or in the region of the hypothalamus-thalamus. Less common locations include cerebral hemispheres, cerebral ventricles, velum interpositium, and spinal cord. In adults, the tumor more frequently occurs in the cerebral hemispheres.
   PA of the hypothalamus may produce symptoms related to obesity, diabetes insipidus, and other symptoms of hypothalamic-pituitary dysfunction.
   >95% enhance. 50% nonenhancing cyst, strongly enhancing mural nodule. 40% solid with necrotic centre, heterogeneous enhancement. 10% solid, homogeneous. (Radiographics)

Question 16

2. 15 yo F 4th vent lesion, likely
3. ependymoma
4. medulloblastoma
5. choroid plexus papilloma

Answer 16

2. medulloblastoma - T - most Dx at 3y (avg 6yo). Malignant, invasive, highly cellular embryonal tumor with rapid growth, malignant, invasive, subarachnoid dissemination. Round, dense, 5th ventricular mass (Blackbook). Overal mean age at Dx for all age groups is about 13yo (mean 9yo) with most (77%) presenting before 19yo. When MB occurs in “adults,” variably described in literature as 15-18yo, most (63%) manifest in pts 20-40yo (Radiographics). Also see below.
3. 15 yo F 4th vent lesion, likely (TW)
4. Ependymoma - F - 3rd most common posterior fossa tumor in children after PA and PNET-MB. Bimodal age distribution with major peak 1-5yo, and second smaller peak in mid 30s. Slight male predominance.
5. medulloblastoma - T - most Dx at 3y (avg 6yo). Malignant, invasive, highly cellular embryonal tumor with rapid growth, malignant, invasive, subarachnoid dissemination. Round, dense, 5th ventricular mass (Blackbook). Overal mean age at Dx for all age groups is about 13yo (mean 9yo) with most (77%) presenting before 19yo. When MB occurs in “adults,” variably described in literature as 15-18yo, most (63%) manifest in pts 20-40yo (Radiographics). Also see below.
6. choroid plexus papilloma - F - 4th ventricle more common location in adults (M>F). Lateral ventricular CPPs in infants and children (M=F)
   In children under the age of 15, brain tumors are the most common solid malignancy and 2nd leading cause of cancer death after leukemia.
   According to UTD MB is the most common malignant brain tumor of childhood, accounting for approx 20% of all primary tumors of the CNS among children less than 19yo. Approx 70% Dx before age 20yo, with peak 5-9yo.

Question 17

3. Gelastic seizures a/w

1. tuber cinereum hamartoma (T)

Answer 17

1. tuber cinereum hamartoma – T – Hamartomas of the tubercinereum are the most frequent type of CNS tumor to cause precocious puberty. They contain GnRH neurons and act as ectopic hypothalamic tissue. They may be associated with gelastic seizures (laughing, giggling).

Question 18

4. Osteogenesis imperfecta
5. Type 1 collagen defect
6. Osteoblast defect
7. Osteoclast defect
8. Fibroblast defect

Answer 18

1. Type 1 collagen defect – T – cause of all cases of OI has not been definitely been established. Howeverm mutations in one or the other of 2 genes which code for proteins that form type I collagen (COL1A1 and COL1A2), account for many of the quantitative and qualitative defects in type I collagen seen in OI.

Question 19

1. 14 y.o with headaches and vermian mass. Most likely?
2. Ependymoma
3. Medulloblastoma
4. Choroid plexus papilloma

Answer 19

2. medulloblastoma - T - most Dx at 3y (avg 6yo). Malignant, invasive, highly cellular embryonal tumor with rapid growth, malignant, invasive, subarachnoid dissemination. Round, dense, 5th ventricular mass (Blackbook). Overal mean age at Dx for all age groups is about 13yo (mean 9yo) with most (77%) presenting before 19yo. When MB occurs in “adults,” variably described in literature as 15-18yo, most (63%) manifest in pts 20-40yo (Radiographics). Also see below.
3. 14 y.o with headaches and vermian mass. Most likely? (TW)
4. Ependymoma - F - 3rd most common posterior fossa tumor in children after PA and PNET-MB. Bimodal age distribution with major peak 1-5yo, and second smaller peak in mid 30s. Slight male predominance.
5. medulloblastoma - T - most Dx at 3y (avg 6yo). Malignant, invasive, highly cellular embryonal tumor with rapid growth, malignant, invasive, subarachnoid dissemination. Round, dense, 5th ventricular mass (Blackbook). Overal mean age at Dx for all age groups is about 13yo (mean 9yo) with most (77%) presenting before 19yo. When MB occurs in “adults,” variably described in literature as 15-18yo, most (63%) manifest in pts 20-40yo (Radiographics). Also see below.
6. choroid plexus papilloma - F - 4th ventricle more common location in adults (M>F). Lateral ventricular CPPs in infants and children (M=F)
   See 2007 question.

Question 20

2. Which is the least common renal tumour in children?
3. Clear cell carcinoma
4. Clear cell sarcoma
5. Wilms tumour
6. Rhabdoid
7. Mesoblastic nephroma

Answer 20

1. Clear cell carcinoma – F – in contrast to adults, renal cell carcinoma is rare in childhood. Classification of RCCs: CCC 75-85%; Chromophilic (papillary) 10-15%; Chromophobic 5-10%; Oncocytic uncommon; Collecting duct (Bellini’s duct) very rare.
2. Which is the least common renal tumour in children? (TW)
3. Clear cell carcinoma – F – in contrast to adults, renal cell carcinoma is rare in childhood. Classification of RCCs: CCC 75-85%; Chromophilic (papillary) 10-15%; Chromophobic 5-10%; Oncocytic uncommon; Collecting duct (Bellini’s duct) very rare.
4. Clear cell sarcoma – T – second most common pediatric renal tumor. Less favorable prognosis than Wilm’s.
5. Wilms tumour – T – most common renal malignancy in children.
6. Rhabdoid – T – Rhabdoid tumor of the kidney is a highly malignant renal tumor, occurs most frequently in children less than 2yo, and almost never in those older than 5yo.
7. Mesoblastic nephroma – T – most common renal mass encountered in neonates. Typically encountered during first few months of life (mean age Dx 3/12). Fetal renal hamartoma.

Question 21

6. Ewings sarcoma
   a. 15-20 yo most commonly
   b. Early hepatic metastasis recognised
   c. Differential Chondrosarcoma
   d. Occurs in metaphysis of long bones
   e. Differential is Neuroblastoma

Answer 21

e. Differential is Neuroblastoma - T - see option c.
* LW agree, based on epi facts being so close but technically less correct.

6. Ewings sarcoma (TW)
   a. 15-20 yo most commonly - F - peak age 15yo. 30% <10yo. 39% 11-15yo. 31% >15yo.
   b. Early hepatic metastasis recognised - F - mets to lung, bones, regional lymph nodes in 11-30% at time of diagnosis, in 40-45% within 2 years of diagnosis.
   c. Differential Chondrosarcoma - F - DDx infection, EG, osteosarc, neuroblastoma <5, multiple myeloma (adult), hodgkin, mets. Chondrosarcoma (central): neck of femur, pubic rami, prox humerus, ribs - usually central within medullary canal meta-/diaphysis. Large soft-tissue mass.
   d. Occurs in metaphysis of long bones - F - less commonly in metaphysis. Metadiaphysis 44%, middiaphysis 33%, metaphysis 15%, metaepiphyseal 6%.
   e. Differential is Neuroblastoma - T - see option c.

*LW:
Additional epi facts:
The peak incidence is between 10 to 15 years of age.
However, 30 percent of cases arise in children under the age of 10, and another 30 percent are in adults over the age of 20.
As with many pediatric tumors, there is a slight male predominance.

Question 22

8. Small round cell tumour in kids – least likely
   a. Kidneys
   b. Bone
   c. Eye
   d. Testis
   e. Adrenal

Answer 22

d. Testis - F - but some can get desmoplastic small round tumor in a paratesticular location

8. Small round cell tumour in kids – least likely (TW)
   a. Kidneys - T - Wilms
   b. Bone - T - Ewings
   c. Eye - T - sheets, trabeculae and nest of small blue cells with scant cytoplasm (Retinoblastoma)
   d. Testis - F - but some can get desmoplastic small round tumor in a paratesticular location
   e. Adrenal - T - neuroblastoma
   Owing to their primitive histologic appearance, many childhood tumors have been collectively referred to as small round blue cell tumors. These are characterised by sheets of cells with small, round nuclei. The differential diagnosis of such tumors includes neuroblastoma, lymphoma, rhabdomyosarcoma, Ewing sarcoma, and occasionally Wilms’ tumor.

Question 23

24. Which areas are most affected by mild-moderate hypoxic ischaemic encephalopathy?
    a. Periventicular white matter in neonates
    b. Parietooccipital region at confluence of ACA, PCA, MCA
    c. Corpus callosum
    d. Basal ganglia
    e. Cortical layers

Answer 23

b. Parietooccipital region at confluence of ACA, PCA, MCA - T - ischaemic changes typically occur along arterial border zones, most frequently at this confluence

24. Which areas are most affected by mild-moderate hypoxic ischaemic encephalopathy? (GC)
    a. Periventicular white matter in neonates - F - true if this specified premature babies (deep PVWM is their border zone). But in term infant the watershed shifts to the parasagittal area.
    b. Parietooccipital region at confluence of ACA, PCA, MCA - T - ischaemic changes typically occur along arterial border zones, most frequently at this confluence.
    c. Corpus callosum - F - infarcts involving the corpus callosum are rare, in part because it is a dense WM tract and therefore less sensitive to ischaemic injury than gray matter.
    d. Basal ganglia - F - common site in profound HIE, including putamen and caudate nucleus.
    e. Cortical layers - F - 3rd, 5th and 6th layers affected in generalised cortical necrosis; particularly the sensorimotor and visual cortices, although involvement is often diffuse.
    Sensitivity to hypoxia: neurons > oligodendrocytes > astrocytes > endothelial cells.
    HIE is the result of global rather than focal injury - ie. global hypoperfusion.
    Injury depends on brain maturity, duration and severity of insult:
    - severe HIE in preterm & term babies: deep grey matter; term bubs may also have perirolandic involvement.
    - postnatal severe HIE: diffuse GM injury, relative sparing of perirolandic cortex and posterior circulation structures.
    - profound HIE in older kids/adults: deep GM nuclei, cortices, hippocampus, cerebellum.
    - less profound insults: IVH and PVL (preterm), parasagittal watershed infarcts (term babies, kids, adults).
    [Adelaide notes; HI brain injury, RG 2008]

Question 24

39. Which tumour is associated with Schiller-Duval bodies?
    a. Spermatocytic seminoma
    b. Embryonal
    c. Yolk sac tumour
    d. Teratoma
    e. Choricarcinoma

Answer 24

c. Yolk sac tumour - T - AKA endodermal sinus tumor. Shiller-Duval bodies. Pure yolk sac tumor is the most common malignant testicular GCT in pre-pubertal children. Pure YS is rare in adult, but occurs in 40% of mixed GCTs.

39. Which tumour is associated with Schiller-Duval bodies? (TW)
    a. Spermatocytic seminoma - F - subtype of seminoma, tends to occur in older men 50-60yo. Better prognosis.
    b. Embryonal - F - 20-25% of NSGCTs (ie of the other 50%).
    c. Yolk sac tumour - T - AKA endodermal sinus tumor. Shiller-Duval bodies. Pure yolk sac tumor is the most common malignant testicular GCT in pre-pubertal children. Pure YS is rare in adult, but occurs in 40% of mixed GCTs.
    d. Teratoma - F - 4-10% of GCT. 2nd most common testicular tumour in young boys 5yrs or less.
    e. Choricarcinoma - F - 1-3%. Most aggressive type of GCT. Present in about 10% of mixed GCTs, but is rare in its pure form in the nut
    Classic Seminoma: b-hCG elevated. AFP normal.
    Pure embryonal: b-hCG elevated. AFP normal
    Yolk Sac / endodermal sinus: AFP elevated. Do no produce hCG. Most common pre-pubertal GCT tumor.
    Choriocarcinoma: b-hCG elevated. AFP normal. Most aggressive type of GCT.

Question 25

64. Which is the least common renal tumour in children?
    a. Clear cell sarcoma
    b. Clear cell carcinoma
    c. Wilms tumour
    d. Rhabdoid
    e. Mesoblastic nephroma

Answer 25

b. Clear cell carcinoma – F – in contrast to adults, renal cell carcinoma is rare in childhood. Classification of RCCs: CCC 75-85%; Chromophilic (papillary) 10-15%; Chromophobic 5-10%; Oncocytic uncommon; Collecting duct (Bellini’s duct) very rare.

64. Which is the least common renal tumour in children? (TW)
    a. Clear cell sarcoma – T – second most common pediatric renal tumor. Less favorable prognosis than Wilm’s.
    b. Clear cell carcinoma – F – in contrast to adults, renal cell carcinoma is rare in childhood. Classification of RCCs: CCC 75-85%; Chromophilic (papillary) 10-15%; Chromophobic 5-10%; Oncocytic uncommon; Collecting duct (Bellini’s duct) very rare.
    c. Wilms tumour – T – most common renal malignancy in children
    d. Rhabdoid – T – Rhabdoid tumor of the kidney is a highly malignant renal tumor, occurs most frequently in children less than 2yo, and almost never in those older than 5yo.
    e. Mesoblastic nephroma – T – most common renal mass encountered in neonates. Typically encountered during first few months of life (mean age Dx 3/12). Fetal renal hamartoma.

Question 26

107. Gelastic seizures a/w
     a. tuber cinereum hamartoma (T)
     b. Churg Strauss
     c. Allergic
     d. granula matris

Answer 26

a. tuber cinereum hamartoma - T - Hypothalamic hamartoma is a congenital nonneoplastic heterotopia which may present with precocious puberty or gelastic seizures (laughing), intellectual impairment and psychiatric disturbance. Iso on T1, hyper on T2 without contrast enhancement.