B79 tumors of the kidney

Question 1

What are the benign tumors of the kidney

Answer 1

Papillary adenoma -

• small cortical papillary adenomas are found in 40% of adults and have no clinical consequence at all

Fibroma

• small tumors of fibroblast stromal cells with collagen stroma, also common and totally benign

Oncocytoma

• uncommon, about 10% of renal tumors
• benign tumor of intercalated cells
• associated with specific loss of chromosomes 1, 14, and Y. which distinguish them from malignant tumors.
• oncocyte = cell with lots of mitochondria. makes them very eosinohpilic on staining and brown on gross morphology.
• often has a central stellate scar visible on radiology
• should be resected just incase it is a misdiagnosed chromophobe renal cell carcinoma.

Question 2

What are the malignant tumors of the kidney?

Answer 2

1) In adults, they are Renal Cell Carcinomas, arising from the renal tubular epithelium. These are the main type of adult kidney tumor

• subtypes:
• Clear Cell Carcinoma (CCRCC)
• Papillary renal cell carcinoma
• Chromophobe renal cell carcinoma

2) The rest are Wilms tumors, aka Nephroblastoma. This is the most common tumor of the kidney overall, but usually occurs in children, usually between ages 2 and 5. Also occurs infrequently in adults.

*

Question 3

Etiology of renal clear cell carcinoma

Answer 3

Occurs in 60 yrs or later, about 3% of all cancers.

twice as common in men

risk factors:

• age
• sex
• smoking
• hypertension
• obesity
• hypercholesterolemia
• polycystic kidney disease of chronic dialysis - strongly increases risk.

Question 4

Morphology of renal clear cell carcinoma and associated genetics

Answer 4

Gross morphology:

• Large, cystic, hemorrhagic, necrotic, varigated cut surface. Solid areas are white/yellow/brown.
• Highly invasive, with tendency to invade the renal vein, all the way through the portal and hepative veins into the right hear.

Histology:

• Cells are clear from glycoen and lipid in the cytoplasm.

Genetis

• familial VHL disease leads to multi-organ tumors, most often of the kidney, it is inherited biallelic loss of the VHL gene on chromosome 3, and in some cases inherited translocations of chromosome 3 affecting the gene.
• Sporadic CCRCC also always have VHL gene mutations

Question 5

What is the morphology and histology of Paipllary renal cell carcinoma?

Associated gene mutations?

Answer 5

Forms papillary growth with dysplasic/anaplastic epithelial cells lining the papillae.

These tumors tend to be bilateral and multifocal.

Activating mutations to the MET HGF receptor, or Trisomies of chromosome 7, which increase the gene dosage of MET.

Question 6

What is the morphology of chromophobe renal cell carcinoma?

Associated gene mutations?

How does the prognosis compare to the other types of rcc?

Answer 6

Resembles an oncocytoma, and is distinguished from it by multiple chromosomal losses, of 1, 2, 6, 10, 13, 17, 21

This type has a better prognosis than the other two.

Question 7

What is the clinical presentation of Renal Cell Carcinoma?

Answer 7

Non-secretory tumors most often grow for a long time before being noticed. During this period the only noticeable symptom is painless hematuria, which still only occurs in abou 50% of cases.

Eventually its size causes all or more frequently one or two parts of the triad of: palpable abdominal mass, painless hematuria, and flank pain.

But RCC is very often secretory and produces paraneoplastic syndromes

It can produce: EPO, PTC-rp, ACTH, Renin, and the symptoms of these will be noticed. EPO is the most common, and 5-10% of patients present with polycythemia

It men it can present in rare cases as left sided varicocele as the tumor obstructs the left renal vein, inducing congestion of the left pampiniform plexus.

Question 8

What is the progression of renal cell carcinoma?

Answer 8

Invasive growth, especially into the renal veins, into liver, and into right heart.

Early metastases without clinical symptoms: vertebra, lung, bone, liver, brain.

Staging is based on the TNM system. Involvment of the tumor spread into the renal vein is a bad prognostic factor, increasing hematogenous spread to lungs and bone.

Stage

5-Year Survival Rate

I 81%

II 74%

III 53%

IV 8%

Question 9

What is the etiology of Wilms tumor?

Answer 9

Occurs mostly in young children, 2-5, also in adults.

Occurs in sporadic and familial forms.

Familial forms:

• WAGR syndrome. Wilms tumor, Aniridia, Genital abnormalities, and Retardation
  
  • large deletion of chromosome 11, including the region of WT1.
• Denys-Drash Syndrome
  
  • ​gonal dysgenesis and renal abnormalities
  • Due to specific exon mutations in WT1 gene
• Beckwith-Weidemann syndrome.
  
  • Enlargement of many organs and body segments
  • inolves the loss of normal maternal imprinting (silencing)
  • abnormal imprinting on the WT2 locus, a misnomer for a genetic region that contains about 10 genes, including the IGF-2 gene.
  • Loss of imprinting –> increased IGF-2 dose, organomegaly/bodymegaly.
  • Increased risk of Wilms Tumor, pancreatic tumors, adrenocortical tumors hepatoblastoma, rhabdomyosarcoma.
• Sporadic Wilms tumor cases involve WT1 mutations in adults

Question 10

What is the gross morphology and histology of a Wilms tumor?

Answer 10

Gross morphology:

• Very Large, circumscribed, lobulated mass that is white/gray and solid. hemorrhagic/necrotic sites are present but are the minority.
• 10% are bilateral or multicentric.

Contains multiple cell types and tissues, it is all derived from mesoderm and produces embryonic primitive renal tissue. Has a classic Triphasic combination of cell types.

• Blastemal - sheets of small blue non-descript cells
• Stromal - fibrocytic cells and myxoid stroma.
• Epithelial - abortive glomeruli and tubules.

About 5% have focal sites of anaplastic cells. This correlates with acquired TP53 mutations.

There are two forms, and the tumor can be distinctly one of the two types, or a mix.

• Epithelial type, with tubular structures and primitive glomeruli
• Stromal type, myxoid stroma formation with neoplastic fibroblasts.
• The pure stromal type has a worse prognosis, but it is most often a mixed type.

Question 11

What is the precursor lesion to a Wilms Tumor

Answer 11

A Nephrogenic rest.

These are often found in the parenchyma adjacent to a Wilms tumor.

Identifying a nephrogenic rest in a patient with Wilms tumor increases the liklihood of future developments of WT in both kidneys.

Question 12

Describe the m

Question 13

What is the clinical presentation of Wilms tumor?

Answer 13

Presentation occurs most often because of the massive size of the tumor, and a palpable mass in the childs abdomen.

Less comonnly, there is fever, abdominal pain, hematuria, or obstruction of the intestines.

Question 14

What is the prognosis of a Wilms Tumor?

Answer 14

Generally very good!

Treatment with resection and chemotherapy usually has an excellent response

Anaplastic foci worsens the prognosis, but as long as these foci are totally resected, the prognosis is the same.

Diffuse anaplasia often has spread extrarenally, and has a bad outcome.