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1M-KIDNEY Flashcards

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1
Q

Renal biopsy indiations

A 
o Diagnosis
o Evolution of the disease
o Prognosis
o Treatment
o Renal transplant
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2
Q

Adequate renal biopsy for focal lesions (irregular/ crescentic lesions)

A

10 glomeruli for irregular and crescentic proliferation

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3
Q

Adequate renal biopsy for extensive lesions (Diffuse lesions)

A

Single glomerulus may be sufficient

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4
Q

Accdg to guideline, how many glomeruli should be examined to properly assess the extent of the disease

A

At least 5-10 glomeruli

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5
Q

2 ways of doing renal biopsy

A

o Percutaneous route - using a cutting needle

o Open biopsy - direct exposure of the kidney; wedge sampling of outer cortex

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6
Q

Needles used for renal biopsy

A

o 16-18 gauge for adults

o 18-gauge needle for children

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7
Q

Biopsy specimen should be divided into __ ?

A

o Light microscopy
o Electron microscopy
o Immunofluorescence

● If you have two cores: one will be for EM and the other is for IF and LM.
● If the core is too small: specimen should be divided for EM and IF

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8
Q

Ideally, how many biopsy cores should be obtained when a needle biopsy is performed

A

Two biopsy cores

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9
Q 
● Fixative – 10% formalin
● Routine evaluation
   - H&E
   - PAS
   - Methenamine silver
   - Trichome stain
A

LIGHT MICROSCOPY

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10
Q 
● Fixation
   o Glutaraldehyde solution
● Tissue embedding
   o Epoxy resins
● Stains
   o Toluidine blue or methylene blue
● For ultrastructural study
   o sections double stained with uranyl acetate
and lead citrate
A

ELECTRON MICROSCOPY

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11
Q

Measurement of sample for EM

A

0.5-1 mm in thickness

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12
Q

o Snap frozen in liquid nitrogen or in isopentane cooled on dry ice
o Frozen sections are cut and stained
with specific antibodies and examined under ultraviolet
light using either transmitted or incident illumination.

A

IMMUNOFLUORESCENCE

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13
Q

Direct vs indirect immunofluorescence

A

o Direct immunofluorescence performed on frozen
sections is the simpler, faster, and most satisfactory
method for the routine evaluation of a renal biopsy

o Indirect methods may be used for extra sensitivity or
for a specific antibody

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14
Q

Measurement of sample for IF

A

2–4 μm thick

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15
Q

Immunostaining useful for antibody-mediated acute allograft rejection

A

C4d

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16
Q

Most common cause of idiopathic nephrotic

syndrome in children

A

MINIMAL CHANGE DISEASE

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17
Q

It was suggested to be caused by circulating factors, produced by
lymphocytes that can damage your glomerular
permeability barrier.

A

MINIMAL CHANGE DISEASE

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18
Q

(+) Heavy proteinuria (selective type) - leading to nephrotic syndrome
(+) Microscopic hematuria (<15%)
(+) HTN (<20%)

A

MINIMAL CHANGE DISEASE

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19
Q

LM:

  • normal
  • minimal meningeal prominence/ lipoid nephrosis
  • podocyte hypertrophy may be seen
A

MINIMAL CHANGE DISEASE

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20
Q

IF: negative for immunoglobulins and complements

A

MINIMAL CHANGE DISEASE

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21
Q

EM:

- Extensive podocyte effacement

A

MINIMAL CHANGE DISEASE

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22
Q

T or F: MCD occurs in children and has poor prognosis

A

FALSE

*It has a very good prognosis because children respond to steroids

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23
Q

T or F: Complete remission from MCD is possible

A

TRUE

*Complete remission is common within 8 weeks
of starting corticosteroid therapy.

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24
Q

(+) Proteinuria - nephrotic

(+) High incidence of progressive renal failure

A

FOCAL AND SEGMENTAL

GLOMERULOSCLEROSIS

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25
Usually a result of circulating permeability factors leading to epithelial cell injury.
FOCAL AND SEGMENTAL | GLOMERULOSCLEROSIS
26
Usual causes of FSGS
Drugs, viral infections, | healed glomerulonephritis, and structural adaptive responses.
27
``` LM: more pink areas because of the sclerosis IF: Nonspecific trapping of IgM and C3 in sclerosed segments EM: Extensive foot process effacement ```
FOCAL AND SEGMENTAL | GLOMERULOSCLEROSIS
28
Glomerular disease characterized by subepithelial immune complex deposits and variable basement membrane thickening, without infiltration by inflammatory cells. - More common in adults - Proteinuria - Progression to chronic renal disease
MEMBRANOUS GLOMERULONEPHRITIS | -aka. membranous nephropathy
29
A large majority of MGN cases, this condition occurs in what form?
Primary/idiopathic form
30
LM: Uniform capillary wall thickening, sometimes with spike and dome pattern; stained with PAS IF: IgG and C3 granular deposits EM: Four stages of subepithelial and intramembranous deposits
MEMBRANOUS GLOMERULONEPHRITIS | -aka. membranous nephropathy
31
A clinical syndrome characterized by persistent proteinuria, hypertension, and progressive decline in renal function.
DIABETEC NEPHROPATHY
32
Considered as the leading cause of ESRD,
DIABETEC NEPHROPATHY
33
Earliest manifestation of DIABETEC NEPHROPATHY
Microalbuminuria
34
Most consistent over manifestation of DIABETEC NEPHROPATHY
Proteinuria (nonselective type)
35
LM: Nodular and diffuse mesangial sclerosis; insudative lesions IF: IgG linear staining along capillary walls and tubular basement membranes EM: Diffuse thickening of basement membranes; increased mesangial matrix
DIABETEC NEPHROPATHY
36
What do you call the very prominent nodular pattern present on some Diabetic nephropathies?
Kimmelstiel-Wilson nodules
37
This results from the deposition of circulating immune complexes in the glomerular mesangium, leading to the activation of the complement cascade via the alternative pathway.
IgA Nephropathy/ Berger Disease
38
o Autosomal dominant o (+) Nephritic syndrome o IgA deposition in the mesangium o IF & EM: IgA reactivity and deposition
IgA Nephropathy/ Berger Disease
39
Severe form of GN
CRESCENTIC GLOMERULONEPHRITIS
40
o Rapid progressive loss of renal function o Hematuria, RBC casts, variable proteinuria and severe oliguria o Nephritic syndrome
CRESCENTIC GLOMERULONEPHRITIS
41
Criteria for crescentic glomerulonephritis or RPGN in LM
50% or more glomeruli show crescents
42
``` DDx for CGN LM: unremarkable IF: linear lace-like in GBM EM: Absent deposits Serology: Anti-GBM Ab Comments: No small vessel vasculitis Other assoc: Goodpasture syndrome ```
ANTI-GLOMERULAR BASEMENT MEMBRANE NEPHRITIS
43
``` DDx for CGN LM: unremarkable IF: Absent EM: Absent Serology: ANCA + Comments: Vasculitis Other assoc: Polyangitis ```
PAUCI-IMMUNE GLOMERULONEPHRITIS
44
DDx for CGN LM: Variable mesangial or endocapillary proliferation IF: Present (varies on dse entity) EM : Electron-dense deposits present Serology: ANA, ds-DNA, ASO, cryoglobulins Comments: Vasculitis present (less common) Other assoc: Lupus nephritis, IgA nephropathy, infxn-assoc GN
IMMUNE COMPLEX-MEDIATED GLOMERULOBEPHRITIS
45
o Acute, sudden, suppression of renal function o Tubular epithelial injury o Rapid increase of serum creatinine, oliguria or anuria
ACUTE TUBULAR NECROSIS
46
More common type of Acute tubular necrosis
Ischemic Acute Tubular Necrosis
47
Tubular necrosis seen in patients who underwent hypovolemic shock
ISCHEMIC ACUTE TUBULAR NECROSIS
48
(+) Minimal cellular swelling to denudation and desquamation of tubular cells (+) Hypoperfusion of the kidney • Starts with the most proximal portion of the tubules
ISCHEMIC ACUTE TUBULAR NECROSIS
49
* Chemically induced injury * Extensive necrosis along proximal segments * Glomeruli is spared
TOXIC ACUTE TUBULAR NECROSIS
50
Indications of renal biopsy if renal transplant rejection is present
to evaluate the intensity and nature of the rejection and to predict the potential reversibility of the lesion.
51
Reasons for failure of graft
rejection, nephrotoxicity caused by immunosuppressive drugs or other causes like necrosis, infection, vascular problem or urinary outflow tract
52
Transplant rejection that occurs within minutes or hours after revascularization
HYPERACUTE REJECTION
53
• Abrupt cessation of urine flow • Mottling cyanosis and diminished turgor in graft • Due to interaction of preformed circulating antibodies in the recipient with antigen on donor endothelial cells such as HLA, ABO
HYPERACUTE REJECTION
54
Transplant rejection seen months after the transplant
ACUTE REJECTION
55
Two types of acute rejection
- Antibody mediated rejection | - Acute T-cell mediated rejection
56
Antibody mediated rejection vs. Acute T-cell mediated rejection
ANTIBODY MEDIATED REJECTION - Caused by anti donor specific antibodies (DSA) - Directed against graft endothelium in glomeruli and peritubular capillaries - Glomerular endothelial cell swelling, increase cellularity and fibrin thrombi - Endolithiasis or fibrinoid necrosis ACUTE T CELL MEDIATED REJECTION - Interstitial edema and focal lymphocytic infiltration - Dense lymphocytic plasma cell and monocytic infiltrates - Tubulitis – reliable marker of acute rejection
57
Transplant rejection from several months to several years
CHRONIC REJECTION
58
Most common cause of graft failure after the initial 6-12 months post transplantation
CHRONIC REJECTION
59
- Progressive and irreversible - End stage of repeated episodes of Ab-mediated rej. &/or T-cell mediated rejection - Gradual decrease in renal function - Proteinuria, nephrotic range, hypertension
CHRONIC REJECTION
60
- Congenital dse (seen in infants & children 3-6 y/o) - Classic presentation as abdominal mass - Hematuria, flank pain and hypertension
WILM’S TUMOR/ nephroblastoma
61
Gene involved in Wilm/s tumor
Chromosome 11
62
- Fleshy, solitary, well-circumscribed and soft - Hemorrhage, cystic change and necrosis - Fibrous septation
WILM’S TUMOR/ Nephroblastoma
63
Conditions assoc with the highest risk of Nephroblastoma
- WAGR - Beckwith-Wiedemann Syndrome - Denys-Drash
64
T or F: When Wilm’s tumor is found in adolescents & adults, or at extra renal sites, it has a good prognosis.
FALSE - Significantly worse clinical outcomes
65
Imaging studies: intrarenal mass that displaces and distorts the collecting system; foci of calcification
Wilm’s tumor
66
2 year old child presented with sudden abdominal pain. The mother of the patient stated that the pain started after the child had a fall while playing around. what is your diagnosis and what is the reason behind the pain?
Dx: Wilm’s tumor | Reason for pain: (+) hemorrhage in the mass when the child fell
67
Three histologic components of Nephroblastoma
- Undifferentiated blastema: dark staining cells in aggregates - Mesenchymal/ stromal tissue: spindle cells in between; lighter region - Epithelial tissue: form your tubular structures
68
Immunostaining of WT’s histologic components
- Epithelial elements: keratin, EMA - Mesenchymal elements: Myogenin, desmin - Neural elements (if present): neuron-specific enolase, glial fibrillary acidic protein, and S-100 protein
69
Molecular genetic features of Wilm’s tumor
WT1 in 11p13 - point mutation in Deny-Drash - deletion in WAGR syndrome WT2 in 11p15.5 - Beckwith-Wiedmann syndrome
70
Most common renal tumor in adults
RENAL CELL CARCINOMA
71
An adult male complained of flank pain and hematuria. Upon inspection, an abdominal mass is present. PMH: hypertension PSHx: cigarette smoking Dx?
Renal Cell Carcinoma
72
RCC diagnostic triad
- Hematuria - Abdominal mass - Flank pain
73
Most common manifestation of RCC
Hematuria
74
Most common histologic type of RCC
Clear cell RCC
75
Which histologic type of RCC? - Well-delineated tumor, solid, golden yellow, centered on cortex - (+) Hemorrhage, necrosis, cystic change - Clear cytoplasm, centrally located hyperchromatic nuclei - delicate fibrovascular network
CLEAR CELL RCC
76
Positive immunohistochemical stains for Clear cell RCC
- Keratins and EMA - CD10, PAX2, PAX8 - Co expression of keratin and vimentin: take note bec not present in normal tubular cells - Keratin and PAX 8: determination of metastasis
77
Clear cell RCC: DDx and Negative stains
1. Adrenal cortical carcinoma - RCC is (-) for: inhibin, melan a, sf-1 2. Clear cell CA of the ovary - RCC is (-) for: 34betaE12, ck7 3. Clear cell CA of the thyroid - RCC is (-) for: thyroglobulin, TTF-1 4. Mesothelioma - RCC is (-) for: calretenin, mesothelin, ck5/6
78
Grading System for Clear Cell RCC (& Papillary RCC)
Grade 1: Nucleoli absent/ inconspicuous; basophilic 2: Conspicuous & eosinophilic at x400 3: Conspicuous & eosinophilic at x100 4: Extreme nuclear pleomorphism &/or rhabdoid or sarcomatoid differentiation
79
Second most common type of RCC
Papillary RCC
80
Type 1 vs Type 2 papillary RCC
Type 1: - Tumors that are well-differentiated, encapsulated, cystic that form complex papillary structures Type 2: - High grade renal cell carcinoma that attempts to form papillary structure - We have nuclear grade 4 with only focal papillary formation
81
Gross: well-circumscribed, generally solitary, gray-brown in color, and absent or minimal hemorrhage or necrosis Microscopic: sharply-defined cytoplasmic membrane with abundant cytoplasm, granular, eosinophilic -Has perinuclear clearing
CHROMOPHOBE RENAL CELL CARCINOMA
82
- Centered in the medulla - Have destructive infiltrative growth - They are in tumor cell aggregates trying to infiltrate the stroma with a significant desmoplastic reaction - Considered as high-grade tumor: usually in stage 3 or stage 4 - Extensive and hyperchromatic
COLLECTING DUCT CARCINOMA
83
A high grade tumor that is extensively pleomorphic and hyperchromatic Composed of high grade cells with rhabdoid and cauliform tumor cells
RENAL MEDULLARY CARCINOMA
84
RCC subtype seen in younger patients especially with African descent and sickle cell trait
RENAL MEDULLARY CARCINOMA
85
Strongest prognostic factor for RCC
Staging
86
Usual location for RCC distant metastases
Lungs and bones
87
An important indicator of relapse A predictor of survival especially in clear cell carcinoma
Microscopic grade (/nuclear grade)
88
RCC staging
Primary Tumor (pT) - pTX: primary tumor cannot be assessed - pT0: no evidence of primary tumor - pT1a: ≤ 4 cm, limited to the kidney - pT1b: > 4 cm and ≤ 7 cm, limited to the kidney - pT2a: > 7 cm and ≤ 10 cm, limited to the kidney - pT2b: > 10 cm, limited to the kidney - pT3a: invades renal vein/branches, perirenal fat, renal sinus fat or pelvicaliceal system - pT3b: extends into vena cava below the diaphragm - pT3c: extends into vena cava above the diaphragm or invades vena cava wall - pT4: invades beyond Gerota fascia, including direct extension to adrenal gland
89
Solid tumor with mahogany brown color and central stellate scar
RENAL CELL ONCOCYTOMA
90
Express pncytokeratin, low molecular weight keratin, CD117, and E-cadherin
RENAL CELL ONCOCYTOMA
91
Which histologic type of RCC? - Well-delineated tumor, solid, golden yellow, centered on cortex - (+) Hemorrhage, necrosis, cystic change - Clear cytoplasm, centrally located hyperchromatic nuclei - delicate fibrovascular network
CLEAR CELL RCC
92
Positive immunohistochemical stains for Clear cell RCC
- Keratins and EMA - CD10, PAX2, PAX8 - Co expression of keratin and vimentin: take note bec not present in normal tubular cells - Keratin and PAX 8: determination of metastasis
93
Clear cell RCC: DDx and Negative stains
1. Adrenal cortical carcinoma - RCC is (-) for: inhibin, melan a, sf-1 2. Clear cell CA of the ovary - RCC is (-) for: 34betaE12, ck7 3. Clear cell CA of the thyroid - RCC is (-) for: thyroglobulin, TTF-1 4. Mesothelioma - RCC is (-) for: calretenin, mesothelin, ck5/6
94
Grading System for Clear Cell RCC (& Papillary RCC)
Grade 1: Nucleoli absent/ inconspicuous; basophilic 2: Conspicuous & eosinophilic at x400 3: Conspicuous & eosinophilic at x100 4: Extreme nuclear pleomorphism &/or rhabdoid or sarcomatoid differentiation
95
Second most common type of RCC
Papillary RCC
96
Type 1 vs Type 2 papillary RCC
Type 1: - Tumors that are well-differentiated, encapsulated, cystic that form complex papillary structures Type 2: - High grade renal cell carcinoma that attempts to form papillary structure - We have nuclear grade 4 with only focal papillary formation
97
Gross: well-circumscribed, generally solitary, gray-brown in color, and absent or minimal hemorrhage or necrosis Microscopic: sharply-defined cytoplasmic membrane with abundant cytoplasm, granular, eosinophilic -Has perinuclear clearing
CHROMOPHOBE RENAL CELL CARCINOMA
98
- Centered in the medulla - Have destructive infiltrative growth - They are in tumor cell aggregates trying to infiltrate the stroma with a significant desmoplastic reaction - Considered as high-grade tumor: usually in stage 3 or stage 4 - Extensive and hyperchromatic
COLLECTING DUCT CARCINOMA
99
A high grade tumor that is extensively pleomorphic and hyperchromatic Composed of high grade cells with rhabdoid and cauliform tumor cells
RENAL MEDULLARY CARCINOMA
100
RCC subtype seen in younger patients especially with African descent and sickle cell trait
RENAL MEDULLARY CARCINOMA
101
Strongest prognostic factor for RCC
Staging
102
Usual location for RCC distant metastases
Lungs and bones
103
An important indicator of relapse A predictor of survival especially in clear cell carcinoma
Microscopic grade (/nuclear grade)
104
RCC staging
Primary Tumor (pT) - pTX: primary tumor cannot be assessed - pT0: no evidence of primary tumor - pT1a: ≤ 4 cm, limited to the kidney - pT1b: > 4 cm and ≤ 7 cm, limited to the kidney - pT2a: > 7 cm and ≤ 10 cm, limited to the kidney - pT2b: > 10 cm, limited to the kidney - pT3a: invades renal vein/branches, perirenal fat, renal sinus fat or pelvicaliceal system - pT3b: extends into vena cava below the diaphragm - pT3c: extends into vena cava above the diaphragm or invades vena cava wall - pT4: invades beyond Gerota fascia, including direct extension to adrenal gland
105
Solid tumor with mahogany brown color and central stellate scar
RENAL CELL ONCOCYTOMA
106
Express pancytokeratin, low molecular weight keratin, CD117, and E-cadherin
RENAL CELL ONCOCYTOMA
107
Yellow to brown tumor with focal hemorrhage; 1/3 of patients have tuberculous sclerosis; majority in adults
ANGIOMYOLIPOMA
108
Micro: - Mixture of fatty tissue, vascular structures, and muscular tissues - Irregular due to tortuosity and lack of elastic tissue
ANGIOMYOLIPOMA
109
- Granular tumor - Common in renal pelvis and ureter - Sx: Hematuria - Assoc w/ hydronephrosis & enlargement of ureter
UROTHELIAL CELL CARCINOMA/ Transitional cell CA
110
Greatest risk factor for Urothelial cell CA
Smoking
111
Diagnosis of Urothelial Cell CA
via intravenous retrograde pyelography

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