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Compare papillary adenoma (left) with normal tissue
(right; tubule lumen lined by cuboidal/columnar cells).
*Papillary adenomas (benign) are the same as papillary
carcinomas (malignant) histologically. They are
distinguished by their size (adenomas are small).
B.
Renal Fibroma/Hamartoma
-
Gross: Firm, grey-white tissue in the pyramids
(<1cm)
-
How: Renal interstitial cells proliferate, so
there’s excess fibrous connective tissue.
-
Clinical: Usually found incidentally.
-
Histo: Fibroblast-like cells in the growths.
C.
Oncocytoma—5%
of surgically resected neoplasms.
-
Gross: Mahogany-brown colored lesion with
fibrous core. Usually solitary and
well-encapsulated. Usually don’t infiltrate
surrounding tissue.
-
Histo: These are very pink due to many
mitochondria, which are visible with electron
microscopy. Nuclei are bland(?)-appearing and may
be pleomorphic. The cells are arranged in nests
and tuberculi (ribbons).
-
How: Arise from intercalated cells in
the collecting duct (these are between the cuboidal
and columnar cells).
D.
Angiomyolipoma
-
Gross: Tumors consisting of vessels, smooth muscle,
and fat. These can be small or large, solitary
or multiple (often multiple in tuberous
sclerosis patients). They’re usually
yellow (because of the fat), and can extend into
the perinephric fat and compress the kidney. These
vascular tumors bleed easily.
-
Histo: Thick-walled blood vessels with smooth muscle.
The muscle cells can be pleomorphic, which is
why this is a neoplasm and not a hamartoma.
-
How: 25-50% of angiomyolipoma patients have tuberous
sclerosis. 80% of tuberous sclerosis patients have
angiomyolipoma. So there’s some relationship there.
II. Malignant Kidney Neoplasms
These are classified based on their histology and
associated cytogenetic abnormalities.
A.
Renal cell carcinoma (Renal Cell Carcinoma)
Basics about renal cell carcinoma
-
These represent 1-5% of all visceral cancers. There
are 30,000 new cases of Renal Cell Carcinoma per year,
and 12,000 Renal Cell Carcinoma deaths. It usually
occurs in the elderly (age 50-60), and is 2-3 times
more prevalent in men.
-
Renal Cell Carcinoma arises from the tubular
epithelium.
-
Risk factors include tobacco, obesity, HTN, unopposed
estrogen, asbestos, petroleum products, CRF, cystic
disease, tuberous sclerosis, and heavy metal (<insert
Metallica joke>).
Clinical course of Renal Cell Carcinoma
-
Renal Cell Carcinoma growth is indolent, so it can
grow unnoticed and be asymptomatic until a late stage.
-
Symptoms:
- In 10%, pain, palpable mass, hematuria (due to
papillae pieces breaking off of the tumor)
- constitutional symptoms
- paraneoplastic syndromes (hypercalcemia, HTN,
Cushing’s, polycythemia)
-
Possible lung metastases. The 5-year survival rate is
45-70%
-
Treatment: nephrectomy (while leaving behind as much
functional kidney as possible)
Types of Renal Cell Carcinoma
-
There are a few types, including clear cell Renal Cell
Carcinoma, papillary Renal Cell Carcinoma, chromophobe
Renal Cell Carcinoma. Again, they’re distinguished
based on histology and cytogenetics.
A.
Hereditary syndromes
Most
Renal Cell Carcinoma is sporadic and can be associated
with certain syndromes.
a) Von Hippel-Lindau syndrome (leads
to clear cell carcinoma):
·
VHL
(a tumor suppressor gene on chromosome 3) normally helps
degrade certain proteins. A mutation in VHL leads to
protein accumulation, which aids tumor growth.
·
50-70% of VHL syndrome patients develop multiple Renal
Cell Carcinoma. Other issues include cysts, seizures,
and cerebellar hemangiomas.
·
Patients without VHL syndrome, but who have mutations in
the VHL genes, also get sporadic clear cell carcinoma.
b)
Hereditary clear cell carcinoma
·
VHL
or related gene abnormalities
·
Patients don’t have the other issues found with
Von Hippel-Lindau syndrome.
c)
Hereditary papillary carcinoma
·
Autosomal dominant mutations in MET
protooncogene (which is a tyrosine kinase receptor
for hepatocyte growth factor), leading to
angiogenesis
·
Multiple bilateral Renal Cell Carcinoma occur
Dr.
Das included a summary chart with some more stuff on it
but this is what was in class:
Papillary Renal Cell Carcinoma
(sporadic AND hereditary):
- remember Trisomy 7 (MET is on chromosome 7)
à
MET protooncogene is active
- also, the PRenal Cell Carcinoma oncogene can be
translocated to the X chromosome (t(X;1))
à
unregulated
mitotic checkpoints.
Clear cell Renal Cell Carcinoma
(sporadic AND hereditary):
- Chromosome 3 translocations
- VHL loss, inactivation/mutation, or
hypermethylation
B.
Clear cell carcinoma—most
common Renal Cell Carcinoma (70-80%)
1.
Gross: Usually a solitary, unilateral tumor arising
from the cortex and gravitating towards a pole
of the kidney. Yellow (due to fat and
glycogen in the “clear” cells). The kidney may be
cystic, with tumor cells in the cyst walls. The
tumor can extend outside the kidney.
2.
Histo: CCC consists of nests of neoplastic cells
(clear cytoplasm and central nucleus). The cytoplasm is
clear due to washed out fat vacuoles and glycogen.
Vascular connective tissue between the nests bleeds
easily.
3.
How:
Associated with loss of section of chromosome 3 in 98%
of cases, which leads to loss of VHL gene.
4.
Clinical: It’s often sporadic and associated with
hereditary symptoms. The tumor often grows into
the renal vein and IVC, which can cause tumor
emboli to travel to the heart.
C.
Papillary cell carcinoma—10-15%
of Renal Cell Carcinoma
-
Gross: Multifocal, bilateral lesions. These are
hemorrhagic and may be encapsulated. They may
be large enough to push the kidney to the side.
-
Histo: Papillae.
-
How: Associated with Trisomy 7, 16, 17; loss of
Y; MET protooncogene; PRenal Cell Carcinoma
gene
D.
Chromophobe renal carcinoma—5%
of Renal Cell Carcinoma
1.
Gross: Large, well-encapsulated tumor that can
breach the renal capsule and perinephric fat.
2.
Histo: CRC has distinct “vegetable” cells
(central round nucleus with a halo and cytoplasm that’s
condensed at the periphery) with distinct cell
membranes.
3.
How:
Tumors arise from the collecting duct intercalated
cells. Associated with multiple chromosome losses
and extreme hypodiploidy.
4.
Clinical: Excellent prognosis compared to the
other two (CCC and PCC).
E.
Urothelial carcinoma of renal pelvis—5-10%
of Renal Cell Carcinoma
1.
Gross: The tumor originates in the renal pelvis
and has fingerlike projections. It can be
exophytic or grow into the kidney.
2.
Histo: occurs in the transitional epithelium (“urothelium”).
3.
How:
Arises in the renal pelvis
4.
Clinical: Hematuria (due to fingerlike
projections breaking off). Occurs with concomitant
bladder tumor 50% of the time; may also occur with
ureter and urethral tumors. The 5-year survival rate is
10-60%.
*Just a note: if you see kidneys with multiple
bilateral tumors, think metastatic cancer (often
from the lungs, GI, breast, ovaries, testes).
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Staging Renal Cell Carcinoma
Remember that it’s done using the TNM system (tumor
characteristics, nodal spread, metastases). Dr. Das
focused on the T.
•
T1:
Tumor <7cm, limited to kidney
–
T1a:
tumor <4cm
–
T1b:
tumor >4cm
•
T2:
Tumor >7cm, limited to kidney
•
T3:
Tumor extends into major veins or adrenal gland or
perinephric tissue but not beyond
Gerota’s fascia.
– T3a: tumor directly invades
adrenal gland or perirenal &/or renal sinus fat
– T3b: tumor grossly extends into
renal vein or its branches or vena cava below the
diaphragm
– T3c: tumor grossly extends into
vena cava above the diaphragm or invades wall of vena
cava
•
T4:
Tumor invades beyond Gerota’s fascia
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