1M-KIDNEY Flashcards
Renal biopsy indiations
o Diagnosis o Evolution of the disease o Prognosis o Treatment o Renal transplant
Adequate renal biopsy for focal lesions (irregular/ crescentic lesions)
10 glomeruli for irregular and crescentic proliferation
Adequate renal biopsy for extensive lesions (Diffuse lesions)
Single glomerulus may be sufficient
Accdg to guideline, how many glomeruli should be examined to properly assess the extent of the disease
At least 5-10 glomeruli
2 ways of doing renal biopsy
o Percutaneous route - using a cutting needle
o Open biopsy - direct exposure of the kidney; wedge sampling of outer cortex
Needles used for renal biopsy
o 16-18 gauge for adults
o 18-gauge needle for children
Biopsy specimen should be divided into __ ?
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
Ideally, how many biopsy cores should be obtained when a needle biopsy is performed
Two biopsy cores
● Fixative – 10% formalin ● Routine evaluation - H&E - PAS - Methenamine silver - Trichome stain
LIGHT MICROSCOPY
● 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
ELECTRON MICROSCOPY
Measurement of sample for EM
0.5-1 mm in thickness
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.
IMMUNOFLUORESCENCE
Direct vs indirect immunofluorescence
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
Measurement of sample for IF
2–4 μm thick
Immunostaining useful for antibody-mediated acute allograft rejection
C4d
Most common cause of idiopathic nephrotic
syndrome in children
MINIMAL CHANGE DISEASE
It was suggested to be caused by circulating factors, produced by
lymphocytes that can damage your glomerular
permeability barrier.
MINIMAL CHANGE DISEASE
(+) Heavy proteinuria (selective type) - leading to nephrotic syndrome
(+) Microscopic hematuria (<15%)
(+) HTN (<20%)
MINIMAL CHANGE DISEASE
LM:
- normal
- minimal meningeal prominence/ lipoid nephrosis
- podocyte hypertrophy may be seen
MINIMAL CHANGE DISEASE
IF: negative for immunoglobulins and complements
MINIMAL CHANGE DISEASE
EM:
- Extensive podocyte effacement
MINIMAL CHANGE DISEASE
T or F: MCD occurs in children and has poor prognosis
FALSE
*It has a very good prognosis because children respond to steroids
T or F: Complete remission from MCD is possible
TRUE
*Complete remission is common within 8 weeks
of starting corticosteroid therapy.
(+) Proteinuria - nephrotic
(+) High incidence of progressive renal failure
FOCAL AND SEGMENTAL
GLOMERULOSCLEROSIS
Usually a result of circulating permeability factors leading to epithelial cell injury.
FOCAL AND SEGMENTAL
GLOMERULOSCLEROSIS
Usual causes of FSGS
Drugs, viral infections,
healed glomerulonephritis, and structural adaptive responses.
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
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
A large majority of MGN cases, this condition occurs in what form?
Primary/idiopathic form
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
A clinical syndrome
characterized by persistent proteinuria,
hypertension, and progressive decline in renal function.
DIABETEC NEPHROPATHY
Considered as the leading cause of ESRD,
DIABETEC NEPHROPATHY
Earliest manifestation of DIABETEC NEPHROPATHY
Microalbuminuria
Most consistent over manifestation of DIABETEC NEPHROPATHY
Proteinuria (nonselective type)
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
What do you call the very prominent nodular pattern present on some Diabetic nephropathies?
Kimmelstiel-Wilson nodules
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
o Autosomal dominant
o (+) Nephritic syndrome
o IgA deposition in the mesangium
o IF & EM: IgA reactivity and deposition
IgA Nephropathy/ Berger Disease
Severe form of GN
CRESCENTIC GLOMERULONEPHRITIS
o Rapid progressive loss of renal function
o Hematuria, RBC casts, variable proteinuria and severe oliguria
o Nephritic syndrome
CRESCENTIC GLOMERULONEPHRITIS
Criteria for crescentic glomerulonephritis or RPGN in LM
50% or more glomeruli show crescents
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
DDx for CGN LM: unremarkable IF: Absent EM: Absent Serology: ANCA + Comments: Vasculitis Other assoc: Polyangitis
PAUCI-IMMUNE GLOMERULONEPHRITIS
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
o Acute, sudden, suppression of renal function
o Tubular epithelial injury
o Rapid increase of serum creatinine, oliguria or anuria
ACUTE TUBULAR NECROSIS
More common type of Acute tubular necrosis
Ischemic Acute Tubular Necrosis
Tubular necrosis seen in patients who underwent hypovolemic shock
ISCHEMIC ACUTE TUBULAR NECROSIS
(+) 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
- Chemically induced injury
- Extensive necrosis along proximal segments
- Glomeruli is spared
TOXIC ACUTE TUBULAR NECROSIS
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.
Reasons for failure of graft
rejection, nephrotoxicity caused by immunosuppressive drugs or other causes like necrosis, infection, vascular problem or urinary outflow tract
Transplant rejection that occurs within minutes or hours after revascularization
HYPERACUTE REJECTION
• 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
Transplant rejection seen months after the transplant
ACUTE REJECTION
Two types of acute rejection
- Antibody mediated rejection
- Acute T-cell mediated rejection
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
Transplant rejection from several months to several years
CHRONIC REJECTION
Most common cause of graft failure after the initial 6-12 months post transplantation
CHRONIC REJECTION
- 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
- Congenital dse (seen in infants & children 3-6 y/o)
- Classic presentation as abdominal mass
- Hematuria, flank pain and hypertension
WILM’S TUMOR/ nephroblastoma
Gene involved in Wilm/s tumor
Chromosome 11
- Fleshy, solitary, well-circumscribed and soft
- Hemorrhage, cystic change and necrosis
- Fibrous septation
WILM’S TUMOR/ Nephroblastoma
Conditions assoc with the highest risk of Nephroblastoma
- WAGR
- Beckwith-Wiedemann Syndrome
- Denys-Drash
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
Imaging studies: intrarenal mass that displaces and distorts the collecting system; foci of calcification
Wilm’s tumor
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
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
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
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
Most common renal tumor in adults
RENAL CELL CARCINOMA
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
RCC diagnostic triad
- Hematuria
- Abdominal mass
- Flank pain
Most common manifestation of RCC
Hematuria
Most common histologic type of RCC
Clear cell RCC
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
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
Clear cell RCC: DDx and Negative stains
- Adrenal cortical carcinoma
- RCC is (-) for: inhibin, melan a, sf-1 - Clear cell CA of the ovary
- RCC is (-) for: 34betaE12, ck7 - Clear cell CA of the thyroid
- RCC is (-) for: thyroglobulin, TTF-1 - Mesothelioma
- RCC is (-) for: calretenin, mesothelin, ck5/6
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
Second most common type of RCC
Papillary RCC
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
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
- 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
A high grade tumor that is extensively pleomorphic and hyperchromatic
Composed of high grade cells with rhabdoid and cauliform tumor cells
RENAL MEDULLARY CARCINOMA
RCC subtype seen in younger patients especially with African descent and sickle cell trait
RENAL MEDULLARY CARCINOMA
Strongest prognostic factor for RCC
Staging
Usual location for RCC distant metastases
Lungs and bones
An important indicator of relapse
A predictor of survival especially in clear cell carcinoma
Microscopic grade (/nuclear grade)
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
Solid tumor with mahogany brown color and central stellate scar
RENAL CELL ONCOCYTOMA
Express pncytokeratin, low molecular weight keratin, CD117, and E-cadherin
RENAL CELL ONCOCYTOMA
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
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
Clear cell RCC: DDx and Negative stains
- Adrenal cortical carcinoma
- RCC is (-) for: inhibin, melan a, sf-1 - Clear cell CA of the ovary
- RCC is (-) for: 34betaE12, ck7 - Clear cell CA of the thyroid
- RCC is (-) for: thyroglobulin, TTF-1 - Mesothelioma
- RCC is (-) for: calretenin, mesothelin, ck5/6
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
Second most common type of RCC
Papillary RCC
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
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
- 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
A high grade tumor that is extensively pleomorphic and hyperchromatic
Composed of high grade cells with rhabdoid and cauliform tumor cells
RENAL MEDULLARY CARCINOMA
RCC subtype seen in younger patients especially with African descent and sickle cell trait
RENAL MEDULLARY CARCINOMA
Strongest prognostic factor for RCC
Staging
Usual location for RCC distant metastases
Lungs and bones
An important indicator of relapse
A predictor of survival especially in clear cell carcinoma
Microscopic grade (/nuclear grade)
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
Solid tumor with mahogany brown color and central stellate scar
RENAL CELL ONCOCYTOMA
Express pancytokeratin, low molecular weight keratin, CD117, and E-cadherin
RENAL CELL ONCOCYTOMA
Yellow to brown tumor with focal hemorrhage; 1/3 of patients have tuberculous sclerosis; majority in adults
ANGIOMYOLIPOMA
Micro:
- Mixture of fatty tissue, vascular structures, and muscular tissues
- Irregular due to tortuosity and lack of elastic tissue
ANGIOMYOLIPOMA
- Granular tumor
- Common in renal pelvis and ureter
- Sx: Hematuria
- Assoc w/ hydronephrosis & enlargement of ureter
UROTHELIAL CELL CARCINOMA/ Transitional cell CA
Greatest risk factor for Urothelial cell CA
Smoking
Diagnosis of Urothelial Cell CA
via intravenous retrograde pyelography
