LUT & MGT Flashcards by JENA MARIE RIVERA

Diseases of the Ureters

-Congenital Anomalies

-Tumors and Tumor-Like Lesions

Obstructive Lesions

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Diseases of the Urinary Bladder

Congenital Anomalies
Inflammation
Metaplastic Lesions
Neoplasms
Obstruction

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Diseases of the Urethra

Congenital Anomalies
Regressive Changes
Inflammation and Infections
Vascular Disorders
Spermatic Cord and Paratesticular Tumors
Testicular Tumors
Lesions of Tunica Vaginalis

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Diseases of the Prostate Gland

Inflammation
Benign Enlargement
Neoplasms

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Ureter

Mucosa of these organs is lined by the uniquely

stratified urothelium or transitional epithelium

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Composed of 5-6 layers of cells with oval nuclei with linear nuclear grooves, and a surface layer consisting of umbrella cells with abundant cytoplasm

Ureter mucosa

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Lamina propria in the bladder form a

discontinuous muscularis mucosa

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bladder cancers are staged on the basis of invasion of the

detrusor muscle (muscularis propria)

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due to urine flow obstruction that causes the intravesical pressure to rise

Bladder hypertrophy

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may entrap and obstruct the ureter

Retroperitoneal tumors or fibrosis

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most common cause of hydronephrosis in infants and children

Ureteropelvic junction (UPJ) obstruction

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Cases that present early in life preferentially affect males, are bilateral in 20% of cases, and are often associated with other anomalies

Ureteropelvic junction (UPJ) obstruction

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More common in women and is most often unilateral

Ureteropelvic junction (UPJ) obstruction

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Abnormal organization of smooth muscle bundles or excess stromal deposition of collagen between smooth muscle bundles at the UPJ, or in extrinsic compression of the UPJ by abnormal renal vessels

Ureteropelvic junction (UPJ) obstruction

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Typically of renal origin
Usually small (5 mm in diameter or less)
Impact at loci of ureteral narrowing—ureteropelvic junction, where ureters cross iliac vessels and where
they enter bladder—and cause excruciating “renal colic”

Calculi

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May be congenital or acquired

Strictures

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Urothelial carcinomas arising in ureters
Rarely, benign tumors or fibroepithelial polyps

Tumor (Intrisic)

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Massive hematuria from renal calculi, tumors, or papillary necrosis

Blood Clots

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Interruption of the neural pathways to the bladder

Neurogenic

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Physiologic relaxation of smooth muscle or pressure on ureters at pelvic brim from enlarging fundus

Pregnancy

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Salpingitis, diverticulitis, peritonitis, sclerosing retroperitoneal fibrosis

Periureteral Inflammation

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With pelvic lesions associated with scarring

Endemetriosis

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Cancers of the rectum, bladder, prostate, ovaries, uterus, cervix; lymphomas, sarcomas

Tumor (Extrinsic)

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Intrinsic and extrinsic lesions may obstruct the ureters and may give rise to

hydroureter, hydronephrosis, and pyelonephritis

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results from proximal intrinsic or extrinsic causes (stones, neoplasms etc.)

Unilateral obstruction

arises from distal causes, such as nodular hyperplasia of the prostate

Bilateral obstruction-

Fibrotic proliferative inflammatory process that encases retroperitoneal structures and causes hydronephrosis

Sclerosing Retroperitoneal Fibrosis

- Occurs in middle to late age and is more common in males - IgG4-related disease

Sclerosing Retroperitoneal Fibrosis

Treatment for this disease are: corticosteroids, ureteral stents or surgical extrication of the ureters (ureterolysis)

Sclerosing Retroperitoneal Fibrosis

MORPHOLOGIC FINDING: Fibrous tissue containing a prominent infiltrate of lymphocytes, often with germinal centers, plasma cells (frequently IgG4-positive), and eosinophils

Sclerosing Retroperitoneal Fibrosis

Associated with increased risk of infection or neoplasia

Diseases of the Urinary Bladder

- Most common and serious congenital anomaly - Can lead to ascending pyelonephritis and loss of renal function - Can give rise to congenital vesicouterine fistulae

Diverticula

- Developmental failure in the anterior wall of the abdomen and the bladder - Bladder communicates directly with the abdominal surface - Exposed bladder mucosa may undergo colonic glandular metaplasia and is subject to chronic infection that spreads to the upper urinary tract - Associated with an increased risk of adenocarcinoma in the bladder remnant

Exstrophy of the bladder

- Urachal canal connects the fetal bladder with the allantois and normally is obliterated at birth - Patent urachus creates a fistulous urinary tract connection between the bladder and umbilicus - When only a central region of patent urachus persists, a urachal cyst lined by urothelial or metaplastic glandular epithelium is formed - Urachal cysts are at increased risk for neoplastic transformation (adenocarcinoma)

Urachal Anomalies

Bacterial pyelonephritis is frequently preceded by infection of the urinary bladder, with retrograde spread of microorganisms into the kidneys and their collecting systems

Acute and Chronic Cystitis

bladder calculi, urinary obstruction, diabetes mellitus, instrumentation, and immune deficiency

Acute and Chronic Cystitis

- Most common: E. coli, Proteus, Klebsiella and Enterobacter - Women are more prone due to shorter urethras

Coliform

TB cystitis leading to renal TB

Mycobacteria

Candida and cryptococcal cystitis (immunosuppressed)

Fungal

- Bladder schistosomiasis - More common in african and middle eastern countries

Schistosomiasis haematobium

Hemorrhagic cystitis

BK Virus

Emphysematous cystitis

Clostridium

Viral (adenovirus), Chlamydia and Mycoplasma

Others

Morphologic Findings hyperemia of the mucosa and neutrophilic infiltrate, sometimes associated with exudate

Aute Cystitis

Morphologic Findings caused by persistent acute cystitis associated with mononuclear inflammatory infiltrates

Chronic Cystitis

Morphologic Findings systemic chemotherapy or pelvic irradiation

Iatrogenic Cystitis

Morphologic Findings cyclophosphamide (hemorrhagic cystitis)

Cytotoxic Cystitis

Morphologic Findings infiltration of the submucosa by eosinophils (nonspecific subacute inflammation) and may also be a manifestation of a systemic allergic disorder

Eosinophilic Cystitis

Morphologic Findings presence of lymphoid follicles within the bladder mucosa and underlying wall

Follicular Cystitis

cystitis triad of symptoms

- Frequency (urination every 15 to 20 minutes) - Lower abdominal pain localized over the bladder region or in the suprapubic region - Dysuria (pain or burning on urination)

Infections may be antecedents to pyelonephritis

cystitis

sometimes a secondary complication of an underlying disorder associated with urinary stasis, such as prostatic hypertrophy, cystocele, calculi, or bladder neoplasms

Cystitis

- Disorder of unknown etiology that occurs most frequently in women - Unpleasant sensation (pain, pressure, discomfort) related to the urinary bladder, associated with urinary tract symptoms of >6 weeks duration, in the absence of infection or other identifiable causes

Interstitial Cystitis (Chronic Pelvic Pain Syndrome)

- Intermittent, often severe, suprapubic pain; urinary frequency; urgency; hematuria; and dysuria - Cystoscopic findings: mucosal fissures and punctate hemorrhages (glomerulations)

Interstitial Cystitis (Chronic Pelvic Pain Syndrome)

- Late (classic ulcerative) phase: associated with chronic mucosal ulcers (Hunner ulcers) - Transmural fibrosis may lead to a contracted bladder

Interstitial Cystitis (Chronic Pelvic Pain Syndrome)

- Pathologic findings are non-specific; mast cells are often increased in the submucosa - Clinically mimics interstitial cystitis - Treatment is largely empiric

Interstitial Cystitis (Chronic Pelvic Pain Syndrome)

- Chronic inflammatory reaction that appears to stem from acquired defects in phagocyte function - Arises in the setting of chronic bacterial infection, mostly by E. coli or occasionally Proteus species -Occurs with setting of immunosuppression

Malakoplakia

-Soft yellow, slightly raised mucosal plaque (3-4cm) -Macrophages have abundant granular cytoplasm - Michaelis-Gutmann bodies: deposition of calcium in enlarged lysosomes

Malakoplakia

- Inflammatory lesion resulting from irritation of the bladder mucosa, most commonly as a result of instrumentation (indwelling catheters) - May be mistaken for papillary urothelial carcinoma, both clinically and histologically.

Polypoid Cystitis

- Common lesions of the urinary bladder in which nests of urothelium (von Brunn nests) grow downward into the lamina propria

Cystitis Glandularis and Cystitis Cystica

metaplasia that take on cuboidal or columnar appearance

Cystitis glandularis

epithelial cells retract to produce cystic spaces

Cytitis cystica

- These 2 processes often coexist: cystitis cystica et glandularis - Both variants can arise in the setting of inflammation and metaplasia - Extensive and multifocal intestinal metaplasia is a precursor to adenocarcinoma

Cytitis cystica Cystitis glandularis

- Response to chronic injury - Urothelium is often replaced by non- keratinizing or keratinizing squamous epithelium, which is a more durable lining

Squamous Metaplasia

- Extensive multifocal keratinizing squamous metaplasia is a precursor to dysplastic lesions and in situ and invasive squamous cell CA - Seen with bladder schistosomiasis

Squamous Metaplasia

- May not be a form of true metaplasia - Some of these lesions are caused by implantation and growth of renal tubular cells at sites of bladder mucosa erosion

Nephrogenic adenoma

- Overlying urothelium is focally replaced by cuboidal epithelium (papillary pattern) - Larger lesions can raise a suspicion of cancer

Nephrogenic adenoma

is the ninth most common cancer type worldwide and is responsible for significant morbidity and mortality

Bladder cancer

*95% of bladder tumors are of _________, with _________ being by far the most common type followed by _____ and ____________

epithelial origin urothelial neoplasms squamous glandular neoplasms

- Non-invasive tumors - Infiltrating urothelial carcinoma - Variants: nested, microcystic, micropapillary, plasmacytoid, sarcomatoid, giant cell, poorly differentiated, lipid-rich, and clear cell

Urothelial (transitional) tumors

- Adenocarcinoma - Squamous cell carcinoma - Mixed carcinoma - Small-cell carcinoma - Sarcomas

Other tumors of the bladder

- Represent about 90% of all bladder tumors - May be seen at any site where there is urothelium, from the renal pelvis to the distal urethra

Urothelial Neoplasms

most common precursor lesions which originate from papillary urothelial hyperplasia

Non-invasive papillary tumors

other precursor lesion to invasive carcinoma (CIS)

Flat non-invasive urothelial carcinoma

term used to describe epithelial lesions that have the cytologic features of malignancy but are confined to the epithelium, showing no evidence of basement membrane invasion

Carcinoma in-situ

* Although invasion into the lamina propria worsens the prognosis, the major decrease in survival is associated with invasion of the _______

muscularis propria (detrusor muscle)

- higher in men (male-to-female ratio of 3: 1), in higher income nations, and in urban dwellers - About 80% of patients are between 50 and 80 years of age - ______ is not familial

neoplas, bladder cancer

Several factors : - Cigarette smoking - Industrial exposure to aryl amines (2-naphthylamine) - Schistosoma haematobium - Long-term use of analgesics - Heavy long-term exposure to cyclophosphamide - Pelvic irradiation

Urothelial Neoplasms

gain-of-function alterations that increase signaling through growth factor receptor pathways

Non–muscle-invasive papillary cancers

- Amplifications of the FGFR3 tyrosine kinase receptor gene - Activating mutations in the genes encoding RAS and PI3-kinase - These tumors frequently recur but progress to muscle- invasive bladder cancer in only about 20% of cases

Urothelial Neoplasms

Flat CIS

majority of muscle-invasive bladder cancers

- Gross: can be purely papillary to nodular or flat - Papillary lesions are red, elevated excrescences (1-5 cm) - Multiple discrete tumors are often present

Urothelial Neoplasms

- Represent 1% of bladder tumors and are often seen in younger patients - Typically arise singly as small (0.5 to 2 cm)

Papilloma

delicate structures superficially attached to the mucosa by a stalk

Exophytic papillomas

- Finger-like papillae covered by epithelium that is histologically identical to normal urothelium - Recurrences and progression are rare but may occur

Papillomas

completely benign lesions consisting of inter-anastomosing cords of cytologically bland urothelium that extend down into the lamina propria; they simulate an invasive process

Inverted papillomas

- Histologically similar with papillomas, differing only in having thicker urothelium with greater density of cells - Tend to be larger than papillomas and may be indistinguishable from papillary cancers - Progression to tumors of higher grade may occur but is rare

Papillary urothelial neoplasms of low malignant potential (PUNLMP)

- Orderly architectural appearance and low- grade cytologic atypia - Cells are evenly spaced (maintain polarity) and cohesive - Scattered hyperchromatic nuclei, infrequent mitotic figures toward the base, and slight variation in nuclear size and shape - May recur and, infrequently, may also invade

Low-grade papillary urothelial carcinomas

- Contain dyscohesive cells with large hyperchromatic nuclei, irregular nuclear chromatin, and prominent nucleoli - Highly anaplastic with mitotic figures - There is disarray and loss of polarity - Can progress to muscle-invasive bladder cancer and metastasis to regional LN and systemic spread (and lung)

High-grade papillary urothelial carcinomas

- Defined by the presence of cytologically malignant cells within a flat urothelium - May range from full-thickness cytologic atypia to scattered malignant cells (pagetoid spread) - Common feature shared with highgrade papillary urothelial carcinoma is a lack of cohesiveness, which leads to shedding of malignant cells into the urine

Flat urothelial carcinoma (CIS)

- Cystoscopy: area of mucosal reddening, granularity, or thickening - Commonly multifocal and may involve most of the bladder surface and extend into the ureters and urethra - If untreated, it progresses to invasive cancer

Flat urothelial carcinoma (CIS)

- Associated with papillary urothelial cancer, usually high grade, or adjacent CIS - Extent of spread (stage), based primarily on depth of invasion in the bladder wall - Invasion of the muscularis propria layer is an indication for radical cystectomy or radiation therapy with neoadjuvant or adjuvant chemotherapy

Invasive urothelial carcinoma

- Urothelial proliferation of uncertain malignant potential (flat hyperplasia) - Urothelial dysplasia - Urothelial carcinoma in situ

Flat Lesions

- Papilloma - Urothelial proliferation of uncertain malignant potential (papillary hyperplasia) - Papillary urothelial neoplasms of low malignant potential - Papillary urothelial carcinoma, low grade - Papillary urothelial carcinoma, high grade

Exophytic Papillary Lesions

- Painless hematuria is the most common symptom of bladder cancer - Frequency, urgency, and dysuria may accompany hematuria - Obstruction of the ureteral orifice may lead to pyelonephritis or hydronephrosis.

Urothelial Neoplasm

Initial treatment of non–muscle-invasive tumors

- Localized low-grade papillary tumors- diagnostic transurethral resection is the only procedure needed - CIS and large, high grade, multifocal, recurrence, or are associated with lamina propria invasion are treated with intravesical instillation of an attenuated strain of BCG

radical cystectomy or cystoprostatectomy, or radiation with chemotherapy

Muscle-invasive bladder carcinoma

Radical cystectomy is also indicated in cases of:

- CIS or high-grade papillary cancer refractory to BCG and other intravesical therapies - CIS extending into the prostatic urethra and ducts - Occasional cases of non–muscle-invasive papillary urothelial high-grade carcinoma

Most metastatic tumors respond poorly to chemotherapy, which produces 5-year survival rates of only _____

15%

- Make up 3% to 7% of bladder cancers - Much more frequent in countries where urinary schistosomiasis is endemic - Arise from atypical keratinizing mucosa (squamous dysplasia and CIS) - Always associated with chronic bladder irritation and infection

Squamous Cell CA

- More frequent than pure squamous cell CA - Most are invasive, fungating tumors or are infiltrative and ulcerative - Can produce abundant keratin to anaplastic tumors with only focal evidence of squamous differentiation

Mixed urothelial carcinoma with areas of squamous carcinoma

- Rare and histologically identical to adenocarcinomas seen in the GIT - Some arise from urachal remnants or in association w/ extensive intestinal metaplasia

Adenocarcinoma

- Indistinguishable from small-cell carcinomas of the lung, occasionally arise in the bladder, often in association with urothelial, squamous, or adenocarcinoma - Strongly associated with loss-of-function of TP53 and RB tumor suppressor genes

Small Cell Carcinoma

- Most common is leiomyoma - They tend to grow as isolated, intramural (submucosal), encapsulated, ovalto-spherical masses up to several centimeters in diameter.

Benign Tumors

- Inflammatory myofibroblastic tumors and various carcinomas that assume sarcomatoid growth patterns are more common - Large masses (15 cm in diameter) that protrude into the vesicle lumen - Soft, fleshy, gray-white gross appearance - Most common bladder sarcoma in infancy or childhood is embryonal rhabdomyosarcoma - Polypoid grape-like mass (sarcoma botryoides)

Sarcoma

secondary malignant involvement of the bladder is most often due to direct extension of cancers arising in adjacent organs, mainly the cervix, uterus, prostate, and rectum

Secondary Tumors

Obstruction of the bladder outlet is of major clinical importance because of its eventual effect on the kidney - Males- ________ - Females- __________

benign prostatic hyperplasia (BPH) cystocele of the bladder

- Congenital urethral strictures - Inflammatory urethral strictures - Inflammatory fibrosis and contraction of the bladder - Bladder tumors, either benign or malignant - Invasion of the bladder neck by tumors arising in contiguous organs - Mechanical obstructions by foreign bodies and calculi - Injury of nerves controlling bladder contraction (neurogenic bladder)

Obstruction of Bladder Outlet Causes

MORPHOLOGIC FINDINGS - Early stages: there is only thickening of the bladder wall due to smooth muscle hypertrophy - Trabeculation of the bladder wall due to progressive hypertrophy - Crypts form and may be converted into diverticula - Enlarged bladder may reach the brim of the pelvis or umbilicus

Bladder Outlet Obstructions

earliest manifestations of venereal infection

Gonococcal Urethritis

common and can be caused by several different organisms

Nongonococcal urethritis

Often accompanied by cystitis in women and by prostatitis in men

Inflammation of Urethra

Reactive arthritis (Reiter syndrome), which is associated with the clinical triad of _____

arthritis, conjunctivitis, and urethritis

- inflammatory lesion that presents as a small, red, painful mass about the external urethral meatus, typically in older females - It consists of inflamed granulation tissue covered by an intact but friable mucosa, which may ulcerate and bleed with the slightest trauma - Surgical excision affords prompt relief and cure

Urethral caruncle

squamous and urothelial papillomas, inverted urothelial papillomas, and condylomas

Benign Epithelial Tumor

urothelial differentiation and are analogous to those occurring within the bladder

Proximal Urethra

squamous cell carcinomas and HPV-related

Distal Urethra

- Malformation of the urethral groove and canal may create an abnormal opening either on the ventral surface of the penis (hypospadias) or on the dorsal surface (epispadias) - Associated with failure of normal descent of the testes and with malformations of urinary tract - Hypospadias- more common of the two - Abnormal opening is often constricted, resulting in urinary tract obstruction and an increased risk of ascending infections - Normal ejaculation and insemination are hampered and may be a cause of sterility

Hypospadias & Epispadias

- Orifice of the prepuce is too small to permit its normal retraction - May result from anomalous development but is more frequently the result of repeated bouts of infection that cause scarring of preputial ring - It interferes with cleanliness, favoring the development of secondary infections and penile carcinoma

Phimosis

Almost invariably involve the glans and prepuce and include a wide variety of specific and nonspecific infections

Penis Inflammation

syphilis, gonorrhea, chancroid, granuloma inguinale, lymphopathia venerea, genital herpes

Specific Infections are STIs

refers to non-specific infection of the glans and prepuce caused by a wide variety of organisms

Balanophostits

- More common agents are C. albicans, anaerobic bacteria, Gardnerella, and pyogenic bacteria - Consequence of poor local hygiene in uncircumcised males - Persistence of such infections leads to inflammatory scarring and, is a common cause of phimosis.

Balanophostitis

benign sexually transmitted wart caused by HPV (serotypes 6 and 11)

Condyloma Acuminatum

- It is related to the common wart and may occur on any moist mucocutaneous surface of the external genitals - May arise in the external genitalia or perineal areas - Penile lesions usually occur in the coronal sulcus and inner surface of the prepuce

Condyloma Acuminatum

Gross: - consist of single or multiple sessile or pedunculated, red papillary excrescences Microscopic: - branching, villous, papillary connective tissue stroma is covered by epithelium with superficial hyperkeratosis and thickening of the underlying epidermis (acanthosis) - Normal orderly maturation of the epithelial cells is preserved - Lining cells frequently display perinuclear cytoplasmic vacuolization (koilocytosis), characteristic of HPV infection

Condyloma Acuminatum

to be reactive rather than neoplastic, is characterized by hard penile plaques that result from the deposition of collagen in the connective tissue between the corpora cavernosa and the tunica albuginea

Peyronie Disease

- Fibrosis is the product of microvascular trauma and subsequent organizing sclerosing chronic inflammation - Results in penile curvature toward the side of the lesion and pain during intercourse - Treatments: surgery and injection of collagenase

Peyronie Disease

- These lesions are encompassed by the umbrella term penile intraepithelial neoplasia (PeIN) - All are squamous lesions confined to the epidermis by an intact basement membrane

Squamous Carcinoma in situ/Penile Intraepithelial Neoplasia

Associated with balanitis xerotica obliterans, occurs on the foreskin of older patients, and as the name implies retains a degree of squamous maturation

Non–HPV-related (differentiated)

- Composed of more overtly malignant cells - May manifest clinically as two distinct lesions:  Bowen disease  Bowenoid papulosis - Both are associated with high-risk HPV (HPV 16)

HPV-related (undifferentiated PeIN)

- Affects the penile shaft and scrotum of older men - Solitary, thickened, gray-white, opaque plaque - When it affects the glans, the lesion acquires a velvety red appearance - Dysplastic squamous cells containing large hyperchromatic irregular nuclei and lacking orderly maturation with atypical numerous mitoses - Gives rise to infiltrating squamous cell carcinoma

Bowen Disease

- Occurs in sexually active adults - It is distinguished from BD by the younger age of affected patients and its presentation as multiple (rather than solitary) reddish brown papular lesions - Virtually never develops into invasive carcinoma and usually regresses spontaneously.

Bowenoid Papulosis

Associated with poor genital hygiene and high-risk HPV infection - Affects middle-aged and older patients (40 to 70 years of age) - Low income status and poor hygiene habits are salient risk factors - Circumcision confers protection, more common in populations in which circumcision is not practiced routinely

Invasive Cell Carcinoma

TRUE OR FALSE Availability of vaccines to both low-risk and high-risk subtypes of HPV may help reduce the incidence of penile cancer and condyloma acuminatum

TRUE

Other risk factors: cigarette smoking and chronic inflammatory conditions such as lichen sclerosis et atrophicus (balanitis xerotica obliterans)