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Flashcards in Urology Path Deck (72)
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31

This is a nephrectomy specimen from a 58-year old man with hematuria. Additionally he had demonstrable polycythemia on CBC. What is his diagnosis and what is causing the polycythemia?

Conventional (clear cell) Renal cell carcinoma

Presentation: – Hematuria
– Few with the classic triad of hematuria, flank pain, and a palpable mass
– Metastasis
Paraneoplastic syndrome: Hypercalcemia, hypertension, polycythemia (produces EPO)
– Incidental finding (CT or MRI) Risk factor is tobacco smoking

• 6th to 7th decade • 2:1 male predominance • Majority of cases are sporadic
• Hereditary cases, like Von Hippel- Lindau (VHL) chromosome 3 (3p) VHL tumor suppressor gene

Grossly: Clear cell RCC: well circumscribed, golden yellow, cystic solid, hemorrhagic, necrosis.

32

Papillary renal cell carcinoma:
Trisomy of chromosome
7 and 17 and loss of Y • Multifocal

Macroscopy: Multifocal tan-white nodules more than 0.5 cm

Microscopy H&E Type 1: papillary and tubular structures covered by small cells with pale cytoplasm with small, oval nuclei and nucleoli. Foamy macrophages are in the papillary vascular cores.

Microscopy H&E Type 2 papillae lined by large cells with abundant eosinophilic cytoplasm. Tumor cell nuclei are large, spherical and contain prominent nucleoli

33

Chromophobe renal cell carcinoma:
- Multiple chromosomal losses (1, Y, 6, 10, 13, 17) and hypodiploidy Differential Diagnosis: Oncocytoma
- Can also have central scar

Gross: mahogany tan or beige- brown, well circumscribed, sometimes with scar (same macroscopy as Oncocytoma)

Histo:H&E stain (Upper right): eosinophilic cytoplasm, hyperchromatic nuclei and perinuclear halos. Visible cytoplasmic membrane

34

Hale's Colloidal Iron Stin:

Chromophobe RCC: stains Colloidal iron positive (top, below)
Oncocytoma RCC: non-staining (bottom)

35

What types of histologic changes are noted in the kidney biopsy below? The patient has a diagnosis of sickle cell trait and demonstrated symptoms of an aggressive invasive cancer (bone mets, lungs mets).

Renal medullary carcinoma:
Risk factors:
- Sickle cell trait, sickle cell disease or hemoglobin SC disease

Aggressive: most patients have extrarenal extension and metastases at presentation
- Dismal prognosis

Renal carcinomas can also be associated with Xp11.2 translocations/ TFE3 Gene Fusion:
- Seen in children, young adults
- Presents at advanced stage but has an indolent clinical course

36


 

Multilocular cystic renal cell carcinoma: 5% adult RCC

- Multi-cystic with small clusters of clear cells
• Excellent prognosis

Gross: multicystic w/o solid tumor, similar to benign multilocular cyst
Histo: Cyst with fluid, thin septae, clear cell lining cysts

37

A 38 year old man develops a painless mass in his testicle. The mass is removed and reveals the following. What is his diagnosis?

Germ cell tumors: 90-95% testicular tumors
• Are the most common tumors in men between 15 and 34 years old
• More common in whites than blacks (5:1)
• Risk factors: – cryptorchidism,
– gonadal dysgenesis and – family history of germ cell tumors (related to the chromosome Xp27)
• Isochromosome12 [i(12p)]
• GCT can show spontaneous tumor regression “testicular scar “ in a patient with metastasis
• Blood tests for GCT: – Lactate Dehydrogenase – alpha-feto protein (AFP) for Yolk Sac tumor (prompt treatment) – beta-human chorionic gonadotrophin (hCG) for choriocarcinoma

Seminomas are radiosensitive and present at an early age
• NSGCT (non-Seminomas)are relatively radiosensitive, more aggressive and usually mixed GCT rather than pure tumors

Classic seminoma: Is the most common adult testicular tumor
- Painless mass in the 4th decade
Gross: bivalved testis: homogeneous, lobulated, soft and pale
HIsto: large polygonal cells with clear cytoplasm (glycogen content) and visible cell membrane, fibrovascular septa with lymphocytes
- Immunohistochemical (IHC) Stains:
– Placentallikealkaline phosphatase (PLAP) +
– CD117(c-kit)+
– OCT3/4 +
20% contain syncytiotrophoblastic cells with a slight increase in beta- human chorionic gonadotrophin (hCG)

38

Spermatocytic seminoma:
• Patients older than 55 y.o.
• It is composed of three size of cells in sheets without fibrovascular septa
• It is not associated with Intratubular Germ Cell Neoplasia
• Excellent prognosis!

39

Non-seminomatous germ cell tumor: embryonal carcinoma

 Aggressive
• Arises from primitive cells
• 3rd and 4th decade
• Pure embryonal carcinoma is rare (2-3%) is present in 80% of Mixed GCT
• 60% of patients present with metastasis
• Pain is a common sign
• Orchiectomy and chemotherapy with survivals above 80%

Grossly: of Embryonal Carcinoma in a bivalved testis: poorly demarcated, variegated with foci of hemorrhage and necrosis

Histo:
Polygonal cells with abundant cytoplasm
• Indistint cell membrane and
• hyperchromatic (dark), pleomorphic, large nucleus.
• Mitosis and necrosis is common.
• Angiolymphatic invasion is common.
IHC markers: CD30, cytokeratins, PLAP, OCT 3/4 and CD117.

40

NSGCT: Yolk sac tumor

• Pure form in the pediatric population before the age of 4 and
• Part of a mixed GCT in adults as a rapidly growing painless mass
• Treatment is orchiectomy and chemotherapy for metastasis or mixed GCT.

Macroscopy of Yolk Sac tumor in a bivalved testis: solid, yellowish, ill defined and glistening

Histo:
The endodermal sinus pattern has Schiller-Duval bodies, which is a fibrovascular papillary formation with cystic cavities liked by cuboidal to columnar cells
- “Hyaline globules” with AFP and alpha-1 antitrypsin
- Alpha fetoprotein

41

NSGCT: teratoma
Composed of tissues of the three germ cell layers: endoderm, mesoderm and ectoderm.
• Second most common tumor in prepuberal testis presenting at 20 months.
• Present in 50% of the mixed GCT • In adults, teratomas are malignant

Histo:
Tissue from all germ layers resembling normal adult tissue
• May show malignant transformation (sarcoma, primitive neuroectodermal tumor, carcinomas) with worse prognosis
• There are no useful markers other than histology and AFP to exclude yolk sac tumor
 

42

NSGCT: choriocarcinoma
• Rare malignant tumor • Marked increase in beta-HCG serum levels
• Presents in the 3rd decade as a component of mixed GCT
• Aggressive with hematogenous spread to the lungs, liver, gastrointestinal tract and brain
• May present as gynecomastia and hyperthyroidism

Gross: hemorrhagic, it can also be a burn out scar (not shown)
Histo:
Cell types: syncytiotrophoblastic, cytotrophoblastic and intermediate trophoblast
- syncytiotrophoblastic are multinucleated (arrow)
- cytotrophoblastic (single nucleus small) and
- intermediate trophoblast (single nucleus larger)
The background is hemorrhagic

43

NSGCT: Mixed Germ cell tumor:
Painless mass
• Serum elevations of AFP (yolk sac) and HCG (choriocarcinoma) are common
• Microscopical components:
– 1st: Embryonal carcinoma
– 2nd: A combination of teratoma with embryonal carcinoma is called “Teratocarcinoma”
– 15% have seminoma

Gross:
 variegated, heterogenous

Histo:
- Embryonal: CD30 + PLAP+
- Teratoma: AFP to exclude Yolk sac tumor
- Seminoma: CD117, PLAP +
- Choriocarcinoma: HCG + AFP + “Schiller-Duval bodies”

Prognosis:
• Lymphovascular invasion is predictive of relapse and lymph node mets
• Metastasis is via lymphatics to the retroperitoneal lymph nodes in contrast to the inguinal lymph node metastasis of other sites of the male genital system

44

Intratubular Germ Cell Neoplasia, Unclassified

• ITGCN is the malignant transformation of the primordial germ cell
• It is precursor of all invasive germ cell tumors except spermatocytic seminoma, pediatric tumors
• Higher incidence in cryptorchid testes and prior GCT
• Prophylactic orchiectomy is recommended

Histo:
absent spermatogenesis. Cells (arrows) with clear cytoplasm and central prominent nucleolus, peritubular fibrosis with a thick basement membrane.
- Tissue marker: PLAP + (brown)

45

Sex cord-gonadal stromal tumors
10% are malignant
Orchiectomy is curative

Leydig cell tumor:
- Testicular swelling
• Can secrete androgens, estrogens, and corticosteroids: – Precocious physical - sexual development and feminization – Gynecomastia
• Two distinct peaks, in childhood and adults 3rd - 6th decade
• Grossly are well circumscribed, from 1 to 10 cm in diameter, yellow to brown, and larger tumors have fibrous trabeculae

Histo: uniform cells with round nuclei and eosinophilic or vacuolated cytoplasm
- crystalloids of Reinke

46

A testicular nodule on a 34 year old man was biopsied. What type of sex cord tumor is shown?

Sex cord gonadal stromal tumor: sertoli

• Testicular mass < age of 40
• Grossly are small (1 to 3 cm), solid, well-circumscribed, yellow–gray nodules
• Large Cell Calcifying Sertoli Cell Tumor (LCCSCT) is a subtype associated with Peutz-Jeghers Syndrome and a component of Carney’s Complex

Histo:
columnar tumor cells arranged into tubules or cords in a fibrous trabecular framework reminiscent of seminiferous tubules

47

Hydronephrosis:
Dilated renal cortex
- Most commonly caused by congenital obstruction of ureteropelvic junction in children
- Most common in males, < 6 months
- Left sided (23-30% bilateral)

48

Nephrolithiasis

Stones in the collecting system of kidney.
- Due to urine concentration with precipitation of minerals
- Most are unilateral, usually in the calyces, renal pelvis, or bladder
- Presents with severe, abrupt flank pain, groin pain, fever, frequency, pain with urination (dysuria), and blood in the urine (hematuria)

49

Urolithiasis: bladder stones

Formation of stones in collecting system of urinary tract

50

Staghorn Calculi= large stones dilating renal pelvis, calices--> cast formation
(Struvite, cystine, uric acid stones)

- **Require treatment**
- Natural history:  Infection, abscess, atrophy, potential for emergent nephrectomy

51

A 35 year old man presents to his physician with flank pain and decreased urine output over the last 2 days. His blood panels reveal a normal serum PTH and calcium. His urinalysis reveals the following (below). Based on his symptoms and the urinalysis, what is his diagnosis and treatment?

Calcium oxalate crystals
Most common
- Calcium oxalate= due to hypercalciuria
- Acidic urine (low pH)
- Calcium oxalate stones are hard and dark
- Urinalysis: calcium oxalate crystals are colorless tetrahedra (envelope shape), oval or dumbbell shapes; polarizable
** seen in ethylene glycol poisoning (antifreeze)

Hypercalcuria (> 200 mg calcium excreted in 24 hrs) due to:
1. Increased intestinal absorption (normal serum PTH, serum Ca but elevated urine Ca)
2. Renal hypercalcuria: slight elevation in serum PTH (can develop osteoporosis over time), normal serum calcium, elevated urine calcium
3. Primary hyperparathyroidism: elevated PTH, elevated serum calcium, elevated urine ca

Treatment:
- Can't be dissolved
1. Ureteral stent (go up urethra)
2. Percutaneous nephrostomy: Go through back into kidney collecting system to drain kidney
3. Extracorporal shock-wave lithotrypsy (ESWL)
4. Ureteroscopy with laser lithotripsy
5. Surgical excision
6. Medical treatment: potassium citrate, thiazide diuretics
7. Observation

52

A 50 year old woman with recurrent UTIs comes to her physician with flank pain. On urinanalsys the following is revealed. What is her diagnosis, what caused this, and what is her treatment?

Struvite stones:
Magnesium ammonium phosphate (15% of stones)
- Due to urea-splitting bacteria (Proteus, Staphylococcus, Providencia)
- Alkaline urine (high pH)
- Triple phosphate crystals in urinalysis are colorless, rectangles or coffin lids shaped

Formed due to Proteus infection (urease-producing bacteria)

Treatment:
1. Surgical removal of all stone burden
2. Correction of anatomic abnormality if possible
3. Culture specific antibiotics
4. IRRIGATE, IRRIGATE, IRRIGATE (if applicable)
5. Long term culture specific antibiotic suppression
- Pen VK 250 mg po daily for 6 mos
6. Acetohydroxamic Acid (urease inhibitor)
- 80% stone growth arrest (vs 40% placebo)
- Multitude of complications: Palpitations, Edema, rash, Nausea, vomit, diarrhea, Headache, loss of taste, hallucination

53

A 50 year old diabetic man comes to the emergency room with flank pain and painful urination. His urinanalysis reveals the following (below). What is his condition? What caused this and what is his treatment?

Uric acid stones:

Causes:
1. Diabetes:
- Higher incidence of uric acid stone formation in type 2 DM stone formers than non-diabetic stone forming pts (34% vs 6%).
- Prevalence of DM or impaired glucose tolerance over 50% in uric acid stone formers.
- MECHANISM:  Insulin resistance at level of PCT leads to defective ammonia production and excessive urine acidity due to unbuffered H+
2. Acidified urine (any cause)

Prevention: Alkalinze patient's urine--> prevent uric acid precipitation
- Also lower uric acid levels in patient's blood to prevent stones

Treatment:
Dietary Modification:
1. Increase fluids (generate 2- 3 Liters urine per day)
2. Limit purine intake ( 6- 8 oz meat per day)
3. Limit sodium (2300 – 3300 mg per day)

Medication
1. Increase uric acid solubility
- Potassium citrate 20 – 60 meq / day
- Sodium bicarbonate 1.3 – 2.6 grams / day
- Stones dissolve 1 cm per month (depends on compliance)
- pH range 6.5 – 7.0
2. Reduce uric acid concentration
- Allopurinol 100 – 300 mg /day (Inhibits enzyme xanthine oxidase)
- Use only if UUA still elevated after urine alkalinized

54

A 4 year old child is admitted to the hospital due to evidence of malnutrition despite adequate diet. Additionally his urinalysis reveals the following accompanied by flank pain. What is his diagnosis and treatment?

Cystine stones:
Rare stone type (1 – 3%)
Autosomal recessive inherited disorder with defective renal transport of dibasic amino acids
- Cystine
- Ornithine
- Lysine
- Argenine
* Cystine poorly soluble in urine (250 mg/ Liter)
See Hexagonal crystals, positive Nitroprusside Test

Treatment:
1. Surgical considerations:  very dense (ESWL resistant)
2. Increase fluids
3. Low methionine diet (meat, eggs; precursor to cystine)
4. Limit sodium (increases renal cystine excretion)
5. Alkalinization (limited role)
6. Chelating Agents
- Captopril
- D-penicillamine (Add pyridoxine to prevent Vit B6 Deficiency)
- Thiola

 

55

A newborn infant has an uncomplicated delivery and the following physical abnormality is revealed. What is his diagnosis and treatment?

Bladder exstrophy with epispadia

Bladder exstrophy:
Absence of anterior bladder wall, anterior abdominal wall
- May be associated with epispadias
- 1:3 M:F ratio

Epispadia:
RARE- Urethra opens on upper side of penis
- Can commonly see entire urethra open along entire shaft
Complicated surgical repair

56

Bladder diverticulum
Pouch-like evaginations of bladder wall
- Seen in males > 55 years
- Requires surgery when associated with infections, stones, perforation

57

A 60-year old woman with a recent e.coli infection presents to her Ob/Gyn with new onset pain with urination. On exam an ulcer is noted in her urethra. A specimen taken from the ulcer reveals the following. What is her diagnosis?

Malakoplakia
Malakos= Soft
Plax= plaque
- Papule, plaque, ulceration of GU tract
- Accumulation of macrophages
- 5-7th decades, females
- Associated with e.coli infection

Histo: Inflammation with large macrophages, eosinophilic cytoplasm with PAS stain

Michaelis-Gutmann bodies (calcifications)
- Engorged lysosomes with bacterial fragments (lysosomal defect)--> calcium salt deposition--> Michaelis Gutman bodies

 

58

Brunn buds/nests:
Type of benign urothelial lesion; associated with chronic inflammation, caliculi

Buds= Normal invaginations of surface urothelium into lamina propria

Nests= similar to buds, urothelial cells have detached from surface, seen within lamina propria

 

59

A 45 year old woman with chronic UTIs has an episode that leads to a biopsy of her bladder for diagnosis. What is her condition called based on the histology below?

Cystitis Cystica
Type of benign urothelial lesion; associated with chronic inflammation, calculi

Cystic dilation of Brunn nests (common)
- See eosinophilic, proteinaceous material in lumen
- Can also be seen in urethra/ureter

60

A newborn infant is physically examined by his physician and the following anomaly is reviewed. What is his diagnosis and treatment?

Hypospadia:
Urethra opens on underside of penis
- Incomplete closure of urethral folds of urogenital sinus
Non-complicated surgical repair