PATH: Renal Neoplasia Flashcards
What is an oncocytoma?
uncommon benign epitheilal neoplasm arising from the intercalated cells of the CD
What genetic changes are seen in oncocytomas?
Loss of chromosomes 1, 14, or Y
What is the gross pathology of an oncocytoma?
Round, Stellate scar visible with imaging, mahogany brown color (tan)
What is the microscopic pathology of an oncocytoma?
abundant cytoplasm with little red bacteria-size dots (that are lots of mitochondria that are there for no reason)
Where are you most likely to find a RCC in the kidney?
cortex
From what cells do RCCs arise?
renal tubular epithelium
Who gets RCC?
Men, around age 64, smokers, HTN, obese, who have occupational exposure to cadmium or have PCKD
How do RCCs like to spread?
through the renal capsule into the perinephric fat and veins (spreading hematogenously)
Where are RCCs most likely to metastasize?
Lung and bone!
What is the most common type of RCC?
Clear Cell carcinoma (65-70%)
What mutation is found in CCC?
AD mutation in von Hippel-Lindau tumor suppressor gene (NEEDS SECOND HIT)
What chromosome is the von Hippel-Lindau gene located on?
chromosome 3
What is the function of the von Hippel-Lindau tumor suppressor gene?
Degrades HIF so that you have less VEGF (if this is mutated, it causes excess VEGF)
What is the gross pathology of CCC?
Solitary
large diameter (well defined) tumors
Yellow color (due to lots of fat)
Tumoral blood vessels prone to rupture (hemorrhage is common)
What is the microscopic pathology of CCC?
- Clear cells with vacuolated lipid-laden cytoplasm OR with granular pink cytoplasm and small/round nuclei
- Lots of small blood vessels present
- “Abortive tubules” may be present
What are the s/s of RCC?
Hematuria, dull flank pain, polycythemia (rare for malignancy!)
What is the prognosis for RCC?
usually remains silent and only is discovered after it metastasizes and causes symptoms
What is the main factor to gauge the prognosis of RCC?
Stage (extent)
Grade (how bad does the nucleus look- clear is lower grade; pink is higher grade)
What is the 2nd most common RCC?
Papillary RCC
What mutation is seen with papillary RCC?
activating mutations in the MET proto-oncogene
What chromosome is the MET proto-oncogene located on?
chromosome 7
What is the function of MET proto-oncogene?
TK receptor for hepatocyte growth factor that spurs abnormal growth of PT epithelial cells
What does the gross pathology of papillary RCC look like?
Mutlifocal and Bilateral
Less yellow (less lipid content)
Necrosis, hemorrhage, cystic degeneration
What does the microscopic pathology of papillary RCC look like?
- Short, nipple-like projections of tumor cells on fibrovascuar stalk
- Cells commonly will have pink cytoplasm
Dialysis will increase the likelihood of what types of RCC?
CCC- 60%
PRCC- 40%
What is the third most common form of RCC?
Chromophobe RCC
What is the cause of chromophobe RCC?
Hypoploidy (loss of entire chromosomes)
Chromophobe RCC comes from what part of the nephron?
intercalated cells of the CD
What is the gross pathology of chromophobe RCC?
-Tan-brown in color
What is the microscopic pathology of chromophobe RCC?
- Large, pale cells with prominent cell membranes
- Nuclei are surrounded by halos of clear cytoplasm
- Tumor cells stain more darkly
- (+) for Hale’s Colloidal iron stain
Which form of RCC has the best prognosis?
Chromophobe RCC has the best prognosis
Other than the renal tubular epithelium, where do other renal primary tumors originate? Why?
urothelium of the renal pelvis (transitional cells). Associated with stones!
What are “transitional cells”?
urothelial cells that look like a transition between a squamous cell and a mucous secreting cell
What is another name for Wilm’s tumor?
nephroblastoma
What is Wilm’s tumor?
uncommon renal neoplasm of young children (ages 2-5)
What is the pathogenesis of Wilm’s tumor?
May arise sporadically or be familial (AD)–tumors derive from mesoderm (blastema cells)
What is the gross pathology of Wilm’s tumor?
- Large, solitary, well-circumscribed mass
- Tan-gray, soft, homogenous tumor with occasional foci of hemorrhage, cystic degeneration , and necrosis
What is the triphasic combination seen in Wilm’s tumor?
1) Blastema cells (small, round, blue)
2) Epithelial cells (forming abortive tubules and glomeruli)
3) Stromal cells (look like fibroblasts)
What are anaplastic cells? Why are they important?
Large, hyperchromatic, pleomorphic nuclei with abnormal mitoses–give a negative prognosis
What are nephrogenic rests?
putative precursor lesions present int he parenchyma adjacent to the tumor (increase risk for WT in contralateral kidney)
What are the S/S of Wilm’s tumor?
Abdominal Mass (pain)
Fever
Hematuria
What is the treatment of Wilm’s tumor?
nephrectomy and chemotherapy (good prognosis unless anaplasia)
What are the 3 syndromes of congenital malformations associated with Wilm’s tumor?
1) WAGR Syndrome
2) Denys-Drash Syndrome
30 Beckwith-Wiedemann Syndrome
What is WAGR syndrome?
Wilms Tumor
Anirida (absence of iris)
Genital Abnormalities
Retardation
What causes WAGR syndrome?
WT1 gene deletions (responsible for normal renal and gonadal development)
What chromosome is WT1 on?
chromosome 11
What is Denys-Drash Syndrome?
Gonadal Dysgenesis + Renal Abnormalities
What causes Dens-Drash syndrome?
dominant negative inactivating mutations of WT1
What is Beckwith-Wiedemann Syndrome?
Enlargement of individual organs (especially on one half of the body) with enlargement of adrenal cortical cells
What causes Beckwith-Wiedemann Syndrome?
Abnormal genomic imprinting of WT2 that normally silences the maternal allele controlling the expression of insulin-like growth factor 2.–> now both paternal (normal) and maternal (not normal) alleles of IGF-2 are expressed (overexpression!!)
