Lecture 13 - Neoplasms of the Kidney

Question 1

Renal Papillary adenomas are small, discrete lesions found in the _____ of the kidney. They arise from ______, and are found incidentally on autopsy in about 22% of cases. Tumors are usually _____ in color.

Answer 1

Cortex

Tubules

Yellow-ish

Question 2

Renal Papillary Adenomas are similar histologically and cytogenetically (associated with Trisomy ___ and ____) to Papillary Carcinoma. What distinguishes their classification?

Answer 2

Size –> less than or equal to 1.5cm = Adenoma.

> 1.5cm = carcinoma bc of likelihood of metastasizing.

Question 3

Angiomyolipomas are tumors comprised of all three tissues suggested by the name. They originate from cells surrounding ______. 25-50% of these patients have _____ _____, which arises from an autosomal dominant _____ of function mutation in the TSC1/2 genes.

Patients can have harmatomas in the brain and skin, so how might they present?

Answer 3

Vessels

Tuberous Sclerosis

Loss of function

They may present with epilepsy, seizures, mental retardation. Keep in mind they have greater susceptibility to spontaneous hemorrhage.

Question 4

Oncocytomas arise from the ______ cells of the ______ _____. Look for cells that are eoisinophilic and have numerous ______. These tumors are well encapsulated and are _______ in color with a central stellate ____.

Answer 4

Intercalated

Collecting Duct

Mitochondria

Mahogany

Central Scar

Question 5

Renal cell Carcinomas account for about _____% of renal cancers in adults. They typically arise in the ____ and ____ decades of life and they are more prevalent in _____ (which gender?).

Answer 5

85%

Sixth and Seventh

Males

Question 6

______ is the most important risk factor for Renal Cell Carcinoma, and _______ is a risk factor especially important in women. Most patients will present with _____, which can be microscopic, though many patients are asymptomatic. About 25% of cases present with metastases. Where are the most common sites for metastases?

Answer 6

Tobacco smoking

Obesity

Lung is the most common, then bone. Regional lymph nodes, liver, adrenals, and the brain are also common.

Question 7

Renal Cell Carcinomas can cause paraneoplastic syndromes from ectopic/excess secretion of hormones, including ______ (leading to polycythemia), ______ (leading to hypercalcemia), and some steroids.

Answer 7

EPO

PTHrP (Parathyroid hormone related peptide)

Question 8

The most common type (70-80%) of the 4 types of Renal Cell Carcinoma (RCC) is _____ cell RCC. It arises from epithelium of the ____ ____ of the nephron. The tumor is _____ in color, and they typically occur as solitary _______ (unilateral or bilateral?) tumors.

Answer 8

Clear Cell RCC

Proximal Tubule

Yellow in color

Unilateral

Question 9

Clear Cell RCC cells have a characteristic clear cytoplasm and the cells are surrounded by “_____ _____” vasculature.

Answer 9

Chicken Wire

Question 10

98% of Clear Cell RCC cases are associated with inactivation of _______ gene on chromosome ____. This gene encodes a protein that’s part of the ubiquitin-ligase complex. Defective ubiquitin-ligase –> high levels of _____ –> overactivation of VEGF –> angiogenesis, cell growth, and metastases.

Answer 10

VHL (von-Hippel-Lindau tumor suppressor gene)

Chromosome 3

HIF-1

Question 11

Some cases of familial Clear Cell RCC caused by VHL mutations can also experience VHL Syndrome. They’ll experience symptoms at a younger age, they are more likely to have cysts in the ____, ____, and _____, they will have BILATERAL multiple RCC, pheocromocytomas, neuroendocrine tumors, and they may have Hemangioblastomas of the CNS (particularly in the _____) as well as in the retina.

Answer 11

Kidney, Liver, and Pancreas

Cerebellum

Question 12

Papillary RCC is the second most common renal cancer. It arises from the ____ ____ of the nephron. Unlike Clear Cell RCC, Papillary RCC tends to be multifocal and ______ (unilateral or bilateral?). They present grossly as hemorrhagic or cystic.

Answer 12

Distal Tubule

Bilateral

Question 13

Papillary RCC can arise from Trisomy ____ and/or ____ (as well as loss of the _____ chromosome). Keep in mind the familial version arises only from trisomy ___. Both familial and sporadic versions result in a mutation of _____ on chromosome 7, which is a proto-oncogene (a tyrosine kinase receptor that binds hepatocyte growth factor.)

Answer 13

7 and/or 17

Loss of the Y chromosome

7

MET

Question 14

Patients with aggressive Papillary RCC can experience Hereditary Leiomyomatosis and RCC Syndrome. This arises from an autosomal dominant mutation of _____ _____ (a krebs cycle enzyme). The patients have Cutaneous and ______ leiomyomas that arise typically in the _____ decade of life.

Answer 14

Fumarate Hydratase

Cutaneous and Uterine Leimyomas

3rd decade

Question 15

Chromophobe RCC is much like Oncocytoma. So does it typically appear bilaterally or unilaterally? Are the cells eosinophilic or basophilic?

Keep in mind this has the best prognosis of all 4 RCCs

Answer 15

It appears mostly Unilaterally.

The cells are Eosinophilic.

Question 16

Chromophobe Carcinoma cells have _____ (thick or thin?) cell membranes, which helps differentiate it from Oncocytoma. Also look for a perinuclear _____, similar to HPV.

Answer 16

Thick cell membranes

Perinuclear Halo

Question 17

Patients with Chromophobe Carcinoma can suffer from Birt-Hogg-Dube Syndrome (keep in mind these patients will be relatively young, about 3rd decade of life). It is caused by an autosomal dominant mutation of BHD gene that expresses ______ (the gene is on the short arm of chromosome _____). Be on the lookout for patients presenting with _______ (small fibrous tumors of hair follicles) and/or _____ cysts/blebs, which may result in pneumothorax.

Answer 17

Folliculin

17

Fibrofolliculomas

Pulmonary cysts/blebs

Question 18

____ ____ Carcinomas are rare, accounting for < 1% of RCCs. Which area of the kidney are these typically located, cortex or medulla?

These are usually ____ (unifocal or bifocal?), but are aggressive, with > 50% of cases having mets.

Answer 18

Collecting Duct Carcinoma

In the Medulla

Unifocal

Question 19

Collecting Duct Carcinomas exhibit a ______ morphology on histology (so think long, rod-like cell formation.)

Answer 19

Tubulopapillary

Question 20

Prognosis for RCC is very high, about ____% 5 year survival in the absence of mets. The overall 5 year survival is about 70%. With invasion of ___ Vein or _____ Fat, it drops to about ____%. Depending on the case, patients can be treated with radical or partial ______.

Answer 20

95% in absence of mets

Renal Vein

Perinephric fat

60%

Nephrectomy

Question 21

Urothelial Carcinoma of the renal pelvis originates from Urothelium of the renal pelvis. About 50% of cases will have concomitant tumors of the ______, while 20% of cases develop subsquent tumors there. Look for these patients to present with ______, and occasionally hydronephrosis with flank pain if the tumor blocks urinary outflow.

There’s increased incidence with ____ Syndrome, Smoking, aromatic _____ (in aniline dyes), and long-term cyclophosphamide use.

Answer 21

Bladder

Hematuria

Lynch Syndrome, Smoking, Aromatic Amines, and long-term cyclophosphamide use.

Question 22

Prognosis for Urothelial Carcinoma of the Renal Pelvis differs between high grade and low grade.

High –> 5 year survival rate of about ___%.

Low –> 5 year survival rate between ____-____%.

Answer 22

10%

50%-100%