Week 6: Hereditary renal tumor syndromes Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

What are the primary functions of the kidney?

A

-Waste removal
-Fluid and acid-base balance
-Regulate blood pressure
-Produce active form of vita D
-Control RBC production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Most kidney cancer occurs in what part of the kidney?

A

The cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

T/F cancer in the medulla of the kidney is common

A

False, most occur in the cortex and cancer in the medulla is rare

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Cancers in the renal pelvis may be associated with what tumor predisposition syndrome?

A

Lynch syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the median age of diagnosis for renal cancer?

A

64 yrs

Unusual in individuals under 45yrs, rare in children

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Is renal cancer more common in men or women? Does it have higher incidence in any ancestry?

A
  • 2-fold more common in men than women
    -Higher incidence in African Americans and Native American populations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are some signs and symptoms associated with renal cancer?

A

-Hematuria (blood in urine)
-Flank pain
-Flank mass
-Weight loss
-Fatigue
-Anemia

Most renal cancer detected incidentally on imaging for vague abdominal complaints that may be unrelated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the routine screening method for renal cancer?

A

There isn’t one

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the four types of treatment/surgical options for renal cancer?

A
  1. Observation/active surveillance: masses <4cm, single focus, no extension
  2. Partial nephrectomy: masses >4cm <7cm, multifocal, bilateral
  3. Radical nephrectomy
  4. Adjuvant therapy: for advanced stage disease and aggressive tumors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are some risk factors for kidney cancer?

A

-Smoking
-Hypertension
-Obesity
-Occupational exposures
-Advanced kidney disease
-Sickle cell
-Certain medications
-Family hx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Approximately what percent of renal cancer is due to hereditary predisposition?

A

~4%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are paragangliomas? If someone is found to have one, should they undergo genetic evaluation?

A

PGL: neuroendocrine tumors of sympathetic or parasympathetic autonomic ganglia

Up to 40% of PGLs and PCCs may be due to hereditary predisposition so recommended that all patients with these tumors undergo genetic evaluation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are pheochromocytomas? Should someone with a PCC undergo genetic evaluation?

A

PCC: neuroendocrine tumors of the adrenal gland

Up to 40% of PGLs and PCCs may be due to hereditary predisposition so recommended that all patients with these tumors undergo genetic evaluation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are gastrointestinal stromal tumors (GISTs)?

A

-Rare tumors usually of gastrointestinal mesenchymal origin
-Most of pediatric GISTs show absent SDHB on IHC
-All pediatric GISTs need genetic risk evaluation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the inheritance pattern, gene, and renal tumor type associated with von Hippel-Lindau?

A

-AD
-VHL gene
-Clear cell RCC, hemangioblastomas, pheochromocytomas

-Founder variant R200W found in Chuvash population, not associated with VHL in heterozygous state, associated with AR familial erythrocytosis type II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

When is it recommended to start screening for individual with VHL?

A

Typically before age 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does management look like for VHL?

A

-RCC: “3cm rule”, active surveillance for tumors <3cm, nephron-sparing approach for larger tumors
-HIF2a inhibitor for adults whose disease does not require immediate surgery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Name the gene, inheritance pattern, and tumor type associated with hereditary papillary renal cancer (HPRC)?

A

-Gene: MET
-AD
-Type I papillary RCC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Name the gene, inheritance pattern, and tumor type associated with Birth-Hogg Dube?

A

-Gene: FLCN
-AD
-Chromophobe RCC, oncocytoma, hybrid, fibrofolliculomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the 3 discussed benign renal tumors?

A

-Angiomyolipomas (more common in females)
-Oncocytomas
-Renal adenomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Name the gene, inheritance pattern, and tumor type associated with tuberous sclerosis complex (TSC)?

A

-Gene: TSC1, TSC2
-AD (2/3 de novo)
-Angiomyolipomas, clear cell RCC

21
Q

Name the gene, inheritance pattern, and tumor type associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC)?

A

-Gene: FH
-AD
-Type II papillary RCC, uterine and cutaneous leiomyomas

22
Q

Name the gene, inheritance pattern, and tumor type/ pathology associated with hereditary paraganglioma and pheochromocytoma syndrome (hereditary PPGL)?

A

-Genes: SDHA, SDHB, SDHC, SDHD
-AD, paternal parent of origin transmission due to maternal imprinting
-Clear cell RCC, oncocytic RCC, paragangliomas, pheochromocytomas, GISTs

23
Q

Name the gene, inheritance pattern, and tumor type associated with BAP1 tumor predisposition syndrome?

A

-Gene: BAP1
-AD
-Clear cell RCC, chromophobe RCC,
uveal/cutaneous melanoma, mesothelioma

24
Q

Describe the increased cancer risk for HPRC and the recommended management

A

-Increased risk for multifocal and bilateral papillary renal tumors
-Screening: abdominal MRI every 1-2yrs beginning at 30yr
-Type 1 papillary renal cancer management: “3cm rule”, active surveillance for tumors <3cm, nephron sparing approach for larger tumors
-Therapeutic agents targeting MET pathway being developed

25
Q

Birt-Hogg Dube has an increased risk for what type of non-kidney cancer?

A

Melanoma

Management: skin exam every 6-12 months

26
Q

Birt-Hogg Dube has a high risk for what pulmonary event?

A

-High risk for spontaneous pneumothorax
-High risk for bilateral multifocal pulmonary cysts (70-85%)

Management: avoid smoking, high ambient pressures, radiation exposure

27
Q

Describe the renal cancer risk for Birt-Hogg Dube

A

-High risk for multifocal, bilateral tumors at young age, lifetime risk for renal tumor 25-35%
-7-fold increased risk for RCC

Management: abdominal MRI every 3yr beginning 20yr, RCC: “3cm rule”, nephron-sparing approach for larger tumors

28
Q

What is the leading cause of death for individuals with TSC?

A

CNS tumors leading cause of morbidity and mortality, renal disease second leading cause

29
Q

T/F most cases of TSC are inherited

A

False! 2/3 cases de novo

30
Q

Would you describe TSC as a localized, singular system disorder or a disorder with multisystem involvement?

A

-Multisystem involvement! -Highly variable phenotype, many cases underdiagnosed due to mild symptoms

31
Q

A mutation in TSC1 or TSC2 produces a more severe phenotype? A mutation in which is more likely to be familial?

A

-TSC2 more severe and likely to be de novo
-TSC1 more likely to be familial

32
Q

A contiguous gene deletion of TSC2 and PKD1 on 16p result in what type of phenotype?

A

-Resulting phenotype of TSC and polycystic kidney disease (PKD) is severe
-Usually evident in utero or diagnosed in infancy
-Need to assess for PKD1 deletion if TSC2 deletion is identified

33
Q

What does screening and management look like for TSC?

A

-Screening begins in infancy
-Routine baseline EEGs and early screening for EEG abnormalities
-Avoid contrast with brain MRI unless necessary
-Abdominal MRI surveillance
-mTOR inhibitors for treatment of TSC associated SEGA, LAM, AML

34
Q

List the 3 primary clinical features of HLRCC

A

-Uterine fibroids: ~90% of females, typically seen at young age and require surgery
-Cutaneous leiomyomas
-RCC: highly aggressive papillary type 2 RCC that metastasizes early

35
Q

What does management look like for HLRCC?

A

-Screening for renal tumors beginning at 8-10yr with annual abdominal MRI
-Prompt surgical resection of renal tumors because such aggressive growth

36
Q

Why is HLRCC an exception to the 3cm rule for management?

A

Because tumors are thought to metastasize very early and therefore should be resected widely and promptly

37
Q

Mutations in what gene associated with PPGL syndrome are associated with risk for metastatic disease?

A

SDHB

38
Q

GISTs, typically in the stomach, are associated with mutations in what two genes for hereditary PPGL?

A

SDHA and SDHC mutations

39
Q

What is unique about the inheritance of hereditary PPGL?

A

-It is AD
-SDHD displays a paternal parent of origin transmission due to maternal imprinting
tumor risk only if paternally inherited SDHD mutation*

40
Q

What does screening and management look like for hereditary PPGL?

A

-Screening: beginning at age 6 annual biochemical and clinical surveillance, biennial full body MRI, consider endoscopic evaluation
-Management: early detection and prompt surgical excision, active surveillance and non-surgical approaches are NOT appropriate

41
Q

List some of the tumor risks for someone with BAP1 TPDS

A

-BAP1-inactivated melanocytic tumor (BMIT)
-Uveal melanoma
-Malignant mesothelioma
-Cutaneous melanoma
-RCC
-Basal cell carcinoma
-Possible increased risk for hepatocellular carcinoma, meningioma, thyroid, breast, lung, ovarian

42
Q

T/F Sporadic tumors frequently have BAP1 mutations

A

True

43
Q

What does management and screening look like for BAP1 TPDS?

A

-No consensus guidelines
-UM: annual dilated eye exam with imaging
-Annual full body dermatological exam
-RCC: abdominal ultrasound or MRI

Agents to avoid:
-Arc-welding
-Asbestos
-Smoking
-Prolonged sun exposure
-Routine chest x-ray and CT

44
Q

Inheritance, gene, info about microphthalmia-associated transcription factor (MITF)

A

-AD
-Gene: MITF
-3-5 fold increase for melanoma
-POSSIBLE increased risk for renal cancer, studies not conclusive

-No medical management recommendations to address possible increased risk for renal cancer

45
Q

Clear cell RCC histology is associated with mutations in what genes?

A

VHL, BAP1, TSC1, TSC2, SDHA-D

46
Q

Papillary type 1 RCC histology is associated with mutations in what gene?

A

MET

47
Q

Chromophobe, hybrid, and oncocytoma RCC histology is associated with mutations in what gene?

A

FLCN

48
Q

Papillary type 2 RCC histology is associated with mutations in what gene?

A

FH

49
Q

Oncocytic RCC histology is associated with mutations in what genes?

A

SDHB, SDHC, SDHD

50
Q

Angiomyolipoma RCC histology is associated with mutations in what genes?

A

TSC1, TSC2

51
Q

Why is identifying the renal cancer syndrome important for non-genetics care?

A

Hereditary cancer syndromes affect surgical management considerations!