Neoplasms of kidney, urinary tract, and prostate

Question 1

Oncocytoma (benign)

Answer 1

• Epithelial tumor of the kidney composed of large cells w/ small uniform nuclei and abundant eosinophilic cytoplasm
• Are encapsulated, brown and uniform w/o any yellow areas, necrosis, or hemorrhage
• Lesion is centrally located “star scar” (stellate shape)
• Micro: uniform cells w/ small nuclei and absence of mitotic activity

Question 2

Angiomyolipoma (benign) 1

Answer 2

• Occurs sporadically and in pts w/ tuberous sclerosis (TSC1/2 mutations)
• Tuberous sclerosis is familial disease characterized by brain tumors, leading to epilepsy, retardation, and multiple skin lesions
• Angiomyolipomas tend to be unilateral and solitary if sporadic, and multiple/bilateral if from tuberous sclerosis

Question 3

Angiomyolipoma (benign) 2

Answer 3

• These tumors are well circumscribed and usually in renal cortex
• 3 main components under micro: mature fat, abnormal blood vessels, and spindle cell proliferation that resembles SM
• There are dysmorphic blood vessels w/ SM-like cells radiating out from them
• Hemorrhage is very common (due to dysmorphic blood vessels)

Question 4

Clear cell carcinoma 1

Answer 4

• 75% of all malignant kidney neoplasms, associated w/ KO of VHL tumor suppressor gene
• Carcinomas in kidneys arise from epithelial tubule cells and thus are adenocarcinomas
• Risk factors for CCC: smoking, obesity, uncontrolled HTN
• Clinical presentation: classic triad of hematuria, flank pain, and mass
• May present w/ left sided vericocele (tumor blocks drainage of left spermatic vein into L renal vein)
• Other Sx include nonspecific ab pain, GI complaints, weight loss, paraneoplastic syndrome (EPO, renin, PTHrP, ACTH)

Question 5

Clear cell carcinoma 2

Answer 5

• Possible comorbidities: anemia, HTN, hepatic dysfxn, fever
• Presence of Sx (especially weight loss) suggests poorer prognosis
• Pts w/ hypercalcemia or hepatic dysfxn must be evaluated for possible metastases (bone, brain, lung, liver)
• The tumors also can grow into the lumen of the renal vein and vena cava as a tumor thrombus
• CCC masses are usually solitary and unilateral, usually large, round, and usually w/ fibrous capsule
• They have some yellow areas of fat, and white and grey areas of necrosis

Question 6

Clear cell carcinoma 3

Answer 6

• Micro: large cells w/ clear cytoplasm arranged in solid nests or alveolar structures, the nests being separated by a prominent vascular network
• Gading based on nuclei and how pleomorphic they are (1 being no pleomorphism, 3 being pretty pleomorphic)
• Gade 4 tumors lose their architecture and all the cells become more spindle shaped, pleomorphic and resemble a sarcoma (sarcomatous renal adenocarcinoma)

Question 7

Wilms tumor

Answer 7

• 95% in children under age 10 (2-10 yo typically)
• A nephroblastoma that presents as a palpable mass, can cause hematuria, pain, or failure to thrive
• Tumors are usually unilateral, large and globular
• Micro: undifferentiated (anapestic) small ovoid cells w/ hyper chromatic nuclei and little cytoplasm (composed of blastema- primitive cells that give rise to metanephros and eventually kidney- look like a sea of small blue cells)
• These tumors necrose and have a high mitotic rate (lots of mitotic figures)
• The tumors show tubule-like structures, primitive gloms, and a variety of mesenchymal cells (cartilage, skeletal muscle, and bone)
• Grade is most important prognostic factor (anaplasia = bad)
• These can spread to lung, liver, bone, brain

Question 8

Urothelial carcinoma 1

Answer 8

• Tumors may arise in the urothelium of the renal pelvis, ureters, bladder, and urethra (90% occur in the bladder- AKA bladder CA, but after bladder most commonly found in renal pelvis) and are usually transitional cell CA
• Transitional epithelia found from the papillae to the urethra (female) or membranous urethra (male)
• Risk factors: cigarette smoking is strongest factor
• Sx: almost all pts present w/ microscopic hematuria, and gross painless hematuria in pts over 40 is bladder CA until proven otherwise

Question 9

Urothelial carcinoma 2

Answer 9

• Papillary pathways (below): go from low grade-> high grade-> invasion
• Grade I: papillary structures lined by thickened transitional epithelial cells w/ normal cytologic features
• Grade II is similar to grade I but w/ more abnormal cytologic features
• Grade III: either papillary or solid growth w/ marked cytologic atypia and increased mitotic activity, often w/ squamous and glandular metaplasia

Question 10

Urothelial carcinoma 3

Answer 10

• Flat pathway (CIS): go from high grade (CIS)-> invasive, associated w/ p53 mutations
• Transitional cell carcinoma in situ (usually multifocal: flat lesion w/o obvious gross abnormalities, but the urothelium shows cytologic abnormalities of grade III transitional cell CA (probably precursor to grade III)
• Low grade tumors are often multifocal, tend not to invade/metastasize, whereas high grade tumors will invade and metastasize to LN, lung, bone, liver

Question 11

Adenocarcinoma of prostate 1

Answer 11

• Most often metastasizes to bone (and LNs)
• Associated w/ translocation of ERG gene
• Most common CA in men
• Usually pts present w/ elevation of serum PSA or a nodule on rectal exam in completely ASx men (BPH can also raise PSA)
• Sx occur late in course, and are usually voiding complaints, back pain, or bone pain
• Usually affects the peripheral part of the prostate gland

Question 12

Adenocarcinoma of prostate 2

Answer 12

• Micro: small irregular infiltrating glands lined by a single layer of malignant cells
• The lack of basal cell layer distinguishes these glands from benign glands
• Benign glands will have this basal cell layer (which stains for k903), but prostate CA glands will not
• The glandular cells have large nuclei w/ prominent nucleolus
• Usually pts present w/ grade 3 (small regular glands), grade 4 (increased glandular irregularity) or grade 5 (single cells that do not form glands)