Urology Path Flashcards by Emily Cheston

Urothelial papilloma:
Benign • 2% to 3% of tumors • Exophytic or inverted
• Microscopically: papillary fronds lined by normal urothelium.
• On cystoscopy: single lesion, 2 to 5 cm in diameter

Below: normal urothelium

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Inverted papilloma:
Rare • Nodular mucosal lesions • Trigone area
• Microscopically: cords of urothelium descend into the lamina propria covered by normal urothelium

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Aggressive Carcinoma in situ

Can be adjacent to papillary carcinoma.
• Multiple, red, velvety, flat patches.
• Microscopically: marked cytologic atypia
• Architecturally: flat, variation in nuclear polarity and discohesion
• Associated with subsequent invasive carcinoma

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Bladder specimen- incidental finding (outgrowth of bladder wall)

Diagnosis? Risk for malignancy?

• Papillary Urothelial Neoplasms of Low Malignant Potential (PUNLMP)

Urothelium= translitional epithelium

The least dysplastic with rare mitosis and organized architecture
• Lack of potential for invasion

• Can progress to carcinoma

4th most common cancer
3:1 M:F
Rare <40
Median age 65 - medical comorbidities
Often multifocal
Can involve the urothelium from the renal pelvis to the urethra

Cytogenic abnormalities:
- Deletion of chromosome 9 (9p- or 9q-), 11p, 13p, 14q, or 17p

Risk factors:

Cigarettes
Arsenic exposure

Treatment:
TURBT: transurethral resection of bladder tumor;
- Low risk: observe
- Intermediate: chemo, BCG/maintenance
- High risk: BCG/maintenance
* Recurrence–> radical cystectomy

Chemo: Cisplatin

Surgery:

urinary diversion: ileum connected to ureters
Neobladder/continent diversion: patients may have to self-catheterize

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Bladder papillary frond removed from bladder following hematuria. What is risk of progression/diagnosis? Treatment?

Low Grade Papillary Urothelial Carcinoma (LGPUC)

Some mitosis
Some disorganized architecture
Some cytologic atypia

4th most common cancer
3:1 M:F
Rare <40
Median age 65 - medical comorbidities
Often multifocal
Can involve the urothelium from the renal pelvis to the urethra

Cytogenic abnormalities:
- Deletion of chromosome 9 (9p- or 9q-), 11p, 13p, 14q, or 17p

Risk factors:

Cigarettes
Arsenic exposure

Treatment:
TURBT: transurethral resection of bladder tumor;
- Low risk: observe
- Intermediate: chemo, BCG/maintenance
- High risk: BCG/maintenance
* Recurrence–> radical cystectomy

Chemo: Cisplatin

Surgery:

urinary diversion: ileum connected to ureters
Neobladder/continent diversion: patients may have to self-catheterize

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Bladder papillary frond removed from bladder following hematuria. What is risk of progression/diagnosis? Treatment?

High Grade Papillary Urothelial Carcinoma (HGPUC)

The most dysplastic
• Frequent mitosis
• Disorganized architecture Nuclear atypia similar to Urothelial Carcinoma In Situ

Most common high grade tumor of urothelium

Clinical features:

Hematuria
15% of the cases have regional or distant metastases at presentation
4th most common cancer
3:1 M:F
Rare <40
Median age 65 - medical comorbidities
Often multifocal
Can involve the urothelium from the renal pelvis to the urethra

Cytogenic abnormalities:
- Deletion of chromosome 9 (9p- or 9q-), 11p, 13p, 14q, or 17p

Risk factors:

Cigarettes
Arsenic exposure

Treatment:
TURBT: transurethral resection of bladder tumor;
- Low risk: observe
- Intermediate: chemo, BCG/maintenance
- High risk: BCG/maintenance
* Recurrence–> radical cystectomy

Chemo: Cisplatin

Surgery:

urinary diversion: ileum connected to ureters
Neobladder/continent diversion: patients may have to self-catheterize

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Squamous cell carcinoma:

Associated with Schistosomiasis

Non-urothelial forms of bladder cancer are RARE

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Bladder specimen in young man who had a patent urachus at birth. He has developed hematuria. What is his diagnosis?

Adenocarcinoma of bladder:

originates from urachal remnants in the bladder dome

Non-urothelial forms of bladder cancer are RARE

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Neuroendocrine carcinoma resembles small cell lung carcinoma of the lung, and can be combined with urothelial carcinoma.

Salt and pepper chromatin

Non-urothelial forms of bladder cancer are RARE

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**Rhabdomyosarcoma of bladder**
 Sarcoma botryoides (Children)

Non-urothelial forms of bladder cancer are RARE

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Urethral carcinoma:
Uncommon
• Elderly women 6th and 7th decades
• Distal urethra: Squamous cell carcinoma (seen more in males)
• Proximal urethra: Urothelial carcinoma
• Most tumors have spread at presentation

Worst presentation= ulceration

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Penis carcinoma
Uncircumcised men • 60 year-old • Uncommon in the USA • Pathogenesis:
– Human papillomavirus (HPV) types 16 and 18
– Phimosis and smegma
• Squamous Cell Carcinoma

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Penile intraepithelial neoplasia: squamous cell carcinoma in situ

Bowen disease
– Shaft
– Solitary, sharply demarcated, erythematous (red) or grayish white plaque

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Eythroplasia of Queyrat: Penile intraepithelial neoplasia

Glans and foreskin

manifests as Solitary or multiple, shiny, soft, erythematous (red) plaques.

Histo: nuclei remain large, pleomorphic, with abnormal maturation

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Bowenoid papulosis:
Bowenoid Papulosis of the penis is not a carcinoma
• Young, sexually active men
• HPV type 16 in 80% of patients
• Multiple brownish or violaceous papules

Histo:
Microscopically: sharply demarcated from normal epidermis and thus resembles HPV-induced warts.
• Lesions regress spontaneously and do not progress to invasive carcinoma

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Invasive squamous cell carcinoma of penis

Ulcer, crater, friable hemorrhagic mass
• Exophytic, fungating
• Glans or prepuce and less commonly the penile shaft

Histo:
• Microscopically: well- differentiated keratinizing
• Invasive tumors have a dense chronic inflammation in the dermis

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Verrucous carcinoma of penis

Low-grade Squamous Cell Carcinoma
• Slow-growing
• Exophytic
• Locally aggressive but seldom metastasizes
• Not related to HPV
• Surgical removal is curative

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“Giant Condyloma Acuminata of Buschke and Löwenstein”

Benign condyloma in the anogenital area
• Glans penis
• HPV 6 and 11 (occasional HPV 16 - 18) and p53 overexpression
• Slow growing verrucous plaque
• Locally destructive but seldom metastasize
• Recurs

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Prostatic intraepithelial neoplasia:
PIN is the noninvasive neoplastic transformation of the lining epithelium of preexisting prostatic ducts and acini
• Divided into low grade and high grade (HGPIN)
• PIN precedes invasive cancer by two decades
• 20% median risk of cancer
• Microscopy:
– Dilated branching glands with intraluminal papillary projections
– Lined by crowded, enlarged cell with prominent nucleoli

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Prostate adenocarcinoma

Multicentric on the peripheral zone
Trans-rectal biopsy
Grossly: irregular, yellow– white, indurated nodules

Histo: Glands with conspicuous “nucleoli” that infiltrate the stroma
• Lack architectural organization
Immunohistochemical stain: used to prove that this biopsy is cancer
- Benign glands will have basal cell layer
- Basal cell layer markers are absent in cancer and present in benign glands and HGPIN
- Alpha-methylacyl-CoA racemase (AMCAR) is present in prostate cancer and HGPIN
- “PIN cocktail”
- Use “Gleason grading system” to stage cancer

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Metastatic Prostatic cancer= blastic

Prostate Metastasizes to lymph nodes, bone, lung, and other
• “Osteoblastic” bone lesions in the vertebral column, ribs and pelvic bones (white on X-ray, vs most carcinomas= osteolytic, dark on x-ray)
• Painful and present a clinical problem
• Prostate specific antigen (PSA) and Prostate Specific Acid Phosphatase (PSAP) immunohistochemical stains used to confirm diagnosis

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Below is a nephrectomy specimen from a 2-year old boy with a palpable abdominal mass. What is his diagnosis and what would the histology reveal?

Wilm’s tumor= Nephroblastoma
Embryonal tumor from nephrogenic nests
Abdominal mass does not cross midline
Chromosome 11 (11p); WT1 and WT2 genes overexpressed
- 85% of pediatric renal tumors

Associated with dysmorphic tumor syndromes in 10% of the cases:
– Wilms-Aniridia-genital anomaly-retardation syndrome
– Beckwith-Wiedemann syndrome (abdominal wall defect, macroglossia,macrosomia)
– Hemihypertrophy
– Denys-Drash syndrome (pseudohermaphroditism glomerulopathy)
– Familial nephroblastoma

Gross: Large round demarcated tumor with tan-grey, fleshy, hemorrhagic surface

Histo: Mixture of immature renal elements
Hematoxylin-Eosin (H&E stain): Blastema, Stroma and Epithelia.
- Blastema= small blue cells in solid nests.
- Hypocellular stroma with myxoid spindle cells.
- Epithelia arranged in tubules

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Congenital Mesoblastic Nephroma (CMN)= 2% congenital renal tumors

Also known as fetal, mesenchymal, or leiomyomatous hamartoma
t(12;15)(p13;q25) with the ETV6-NTRK3 fusion gene
Most CNM are benign with 5 -10% recurrences and metastases

Macroscopy: solitary, tan, bulgy, soft mass similar to leiomyomas

Microscopy H&E stain: spindle cells with mitosis on the cellular pattern

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Clear cell sarcoma of kidney: 3.5% pediatric renal tumor
Aggressive malignant sarcoma also known as bone-metastasizing tumor
• Late recurrence and bad prognosis.

Macroscopy: large, located in the medulla

Microscopy H&E stain: epithelioid with
clear cytoplasm and clear nucleus, arranged in sheets with arborizing blood vessels in a myxoid stroma

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**Rhabdoid tumor**= 2.5% pediatric renal tumors - Deletion or mutation of IN11 gene, chromosome 22q11 • Despite the histology it does not have muscle differentiation • Highly malignant with poor prognosis. Associated with a brain tumor: Atypical Rhabdoid Teratoid Tumor • (Below cytology smear H&E stain showing rhabdoid appearance of the cell with excentric nucleus, prominent nucleoli, and abundant eosinophilic cytoplasm) Macroscopy: pale, poorly circumscribed and often has satellite nodules Microscopy H&E stain: high-grade, round cell with abundant cytoplasm

**Oncocytoma**: 6-9% renal cancers in adults Macroscopy of an Oncocytoma: well circumscribed mahogany brown mass with a central scar Renal oncocytoma is thought to arise from the intercalated cells of collecting ducts of the kidney.

**Metanephric adenoma** • Macroscopy (Upper left): gray-tan, well circumscribed but unencapsulated • Microscopy H&E stain (Upper right): tumor (dark color) sharply demarcated (arrow) from the benign (pink); (Left) cells are small, uniform, dark; form branching tubules, papilla or glomeruloid structures in an acellular stroma

**Papillary Adenoma**: Macroscopy: gray-tan, less than or equal to 0.5 cm Microscopy H&E stain: papillary projections of small, bland, basophilic cells or eosinophilic cells. Insert: **Psammoma bodies**

This is a nephrectomy specimen from a 32 year old female with abdominal pain. Paracentesis demonstrated blood. At laparotomy, a renal neoplasm was discovered. What is her diagnosis and how should she be treated?

**Angiomyolipoma**: Female Associated with tuberous sclerosis Co-express melanocytic and muscle markers **Should be removed due to risk of hemorrhage** Gross: yellow (resembling fat) or tan, large and well-circumscribed Microscopy H&E stain 3 components: blood vessels + muscle + fat

**Tuberous Sclerosis Complex**: Mutation on TSC1, TSC2, Chromosomes 9 and 16 - Increased risk of angiomyolipoma **(below**)

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.

**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

* *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

**Hale's Colloidal Iron Stin:** Chromophobe RCC: stains Colloidal iron positive (top, **below)** Oncocytoma RCC: non-staining (bottom)

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

**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

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)

**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!

**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.

**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

**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

**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

**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

**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)**

**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**

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

**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)

**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)

**Urolithiasis: bladder stones** Formation of stones in collecting system of urinary tract

**Staghorn Calculi**= large stones dilating renal pelvis, calices--\> cast formation * *- \*\*Require treatment\*\*** - Natural history: Infection, abscess, atrophy, potential for emergent nephrectomy | (Struvite, cystine, uric acid stones)

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

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

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

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

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

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

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

**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

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

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

A 12-year old boy comes to the pediatrician complaining of genital pain (at the tip of his penis) with the erections he now experiences. Based on the exam below, what is his diagnosis and treatment?

**Phimosis**: Narrowing of prepuce--\> impairs retraction over glans * *Paraphimosis: (below)** narrow prepuce retracted, can strangulate glans (due to infection, trauma) - Both cured by cirumcision

A 55 year old chronic alcoholic has an acute episode of pancreatitis. On hospital admission he begins complaining of abdominal swelling and the following is revealed. What is his diagnosis?

**Scrotal edema** caused by pancreatitis Other causes of scrotal edema: 1. Hydrocele= serous fluid collection in scrotal sac between two layers of tunica vaginalis - Congenital: most common cause of scrotal swelling in infants, associated with inguinal hernia - Acquired: secondary to infection, tumor, trauma; U/S or transluminate fluid--\> can lead to testicular atrophy or fluid can become infected and cause periorchitis 2. Hematocele: accumulation of blood between tunica vaginalis layers due to trauma, hemorrhage into hydrocele, tumor, infection 3. Spermatocele: Cyst in efferent ducts (widened) of rete testis or epididymis - Ressembles paratesticular nodule or fluid-filled mass - Cyst is lined with cuboidal epithelium with spermatozoa in various degenerative stages 4. Varicocele: Dilation of testicular veins - Cause infertility, oligospermia (most asymptomatic) 5. Scrotal inguinal hernia: protrusion of intestines into scrotum through inguinal hernia

What is the diagnosis of this patient's itching in his penis and the complications of this infection?

**Balanitis**: Balanoposthitis due to Candida Balanitis: Glans, due to poor hygeine Balanoposthitis: glans and foreskin; bacteria, fungi Complications: meatal stricture, phimosis, paraphimosis

What is the diagnosis of this patient's penile disfigurement and what is a complicaiton of it?

**Balanitis xerotica obliterans** Chronic inflammatory syndrome of subepithelial connective tissue Xerotica= fibrosis Obliterans= sclerosis Glans= white, indurated - Can cause strictures, phimosis Equivalent to lichen sclerosis atrophicus of vulva

A 30 year old man with a recent bout of Salmonella comes to his PCP because of concerns of a new STD (see below). Additionally he has visible conjunctivitis and symptoms of arthritis in his knees. What is his diagnosis and is there treatment?

**Circinate balanitis**: Circular, linear, or confluent plaque-like discolorations of glans, superficial ulcerations Seen in **Reiter syndrome** * *Reiter syndrome**= urethritis, conjunctivitis, arthritis in weight-bearing joints - can also see circinate balantitis, cervicitis, skin eruptions - Effects adults with HLA-B27 haplotype - Symptoms after chlamydia, Shigella, Salmonella, Campylobacter - Inappropriate immune reaction- spontaneously resolves

**Plasma cell balanitis**: aka Zoon balanitis Chronic disease of unknown origin--\> macular discoloration/painless papules on glans - Infiltration of plasma cells, lymphocytes, epithelial thickening

A 30-year old man comes to the physician with his wife after difficulty conceiving. On physical exam, he is noted to have slight gynecomastia, sparse facial and body hair, and small testes. Sperm analysis reveals few sperm with abnormal motility. Based on the histologic specimen of his testes below, what is his diagnosis?

* *Klinefelter's syndrome infertility** (47XXY) - Hyalinzed seminiferous tubules - Prominent Leydig cells - Results in infterility **Below**: normal seminiferous tubules, Leydig cells

What abnormalities are noted in the sample of seminiferous tubules below?

**Germ cell morphologic alterations**: - Maturation arrest (front) - Germ cell aplasia ("Sertoli cell only syndrome")- below

**Spermatic cord torsion** * Twisting of the spermatic cord with compromise of the testicular blood supply * Etiology: abnormal fixation of the testis and spermatic cord * Seen in children and young adults during vigorous activity * Clinically presents as abrupt onset of pain and swelling **Below**: Histo of testicular infarct following testicular torsion

Below is an orchectomy specimen from a man who developed chronic UTIs. What type of changes have occured in his testicules?

**Granulomatous orchitis** * Gram-negative bacterial orchitis is the most common form, often secondary to urinary tract infection * Syphilitic orchitis * Mumps orchitis unilateral * Granulomatous orchitis type IV (cell-mediated) hypersensitivity reaction and tuberculosis * Malakoplakia **Histo Front**: Multinucleated giant cells (green arrows) and poorly formed granulomas with necrosis **Below**: Ziehl Neelsen stain with acid fast bacilli (black arrow) in RED for tuberculosis

**Prostatitis**: • Cause: coliform uropathogens, but often cannot be determined • May cause elevated serum prostate-specific antigen (PSA) Types of Prostatitis: • Acute Prostatitis • Chronic Bacterial Prostatitis • Nonbacterial Prostatitis • Granulomatous Prostatitis

A 72 year old African American man with increasing issues of urinary hesitancy and feeling of incomplete emptying is autopsied following a massive MI. His prostate is removed (below). Based on the gross appearance of his prostate and his symptoms, what was the pathology and how would he have been treated if his symptoms had progressed? What we he at risk for developing?

* *Benign prostatic hyperplasia**: 1. Mechanical Component - Glandular proliferation 2. Dynamic Component - Baseline tonicity of smooth muscle (activated by alpha receptors) \*\* Prostate enlargement in BPH driven by androgens= dihydrotestosterone (DHT) **Symptoms**: Obstructive symptoms: - Decreased force of stream - **Feeling of incomplete emptying** - Intermittency (double voiding) **- Hesitancy (delay of onset of voiding)** - Need to strain to empty bladder Irritative: - Frequency of urination - Urgency (strong desire to void) - Nocturia (waking to urinate) - Dysuria (pain during urination) - Hematuria (blood in urine) * *Diagnosis:** 1. Assess symptoms: AUA symptom score: - 7 questions: Incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia - Each question has severity (1-5) - Mild= 0-7; moderate= 8-19; severe= 20-35 2. Labs: serum creatinine, PSA, urinalysis, urine culture 3. Check PVR (post-void residual) - Remaining volume after micturation - Transabdominal U/S or catheterization 4. Renal ultrasound: - Check for hydronephrosis, cortical thinning * *Treatment**: 1. Observation 2. Medical management - Alpha blockers - 5-alpha reductase inhibitors 3. Surgery - Various methods of clearing bladder outlet (TURP, etc) * *Indications for surgery: - Refractory urinary retention (may require catheters. - Recurrent UTI - Renal Insufficiency - Bladder calculi - Recurrent gross hematuria from prostate** Risks of surgery: - bleeding, bladder neck contracture - Retrograde ejaculation (30-97%)- usually indicator of treatment effectiveness - Tranurethral syndrome: absorption of hypotonic solution used in TURP procedure (hyponatremia)