Lower Urinary Tract and Male Genital System Diseases

**Double and bifid ureters**

almost invariably associated with totally distinct double renal pelves or with the anomalous development of a large kidney having a partially bifid pelvis terminating in separate ureters

**Ureteropelvic junction (UPJ) obstruction**

a congenital disorder that is the most common cause of hydronephrosis in infants and children.The condition has been ascribed to abnormal organization of smooth muscle bundles at the UPJ, to excess stromal deposition of collagen between smooth muscle bundles, or rarely to congenitally extrinsic compression of the UPJ by renal vessels

**Diverticula**

saccular outpouchings of the ureteral wall,are uncommon lesions that may be congenital or acquired. Most are asymptomatic, but urinary stasis within diverticula sometimes leads to recurrent infections. Dilation (hydroureter), elongation, and tortuosity of the ureters may occur as congenital anomalies or as acquired defects

**Ureteritis**

though associated with inflammation, is typically not associated with infection and is of little clinical consequence

**Primary ureteral tumors**

rare; benign ureteral neoplasms are usually mesenchymal; *fibroepithelial polyps* present as small intraluminal projections, most commonly in childre

**Malignant ureteral neoplasms**

primarily urothelial carcinomas comparable to similar tumors in the renal pelvis and bladder; The majority are *urothelial carcinomas*

**Unilateral obstruction**

typically results from proximal causes, whereas bilateral obstruction arises from distal causes, such as nodular hyperplasia of the prostate

**Sclerosing Retroperitoneal Fibrosis**

uncommon cause of ureteral narrowing or obstruction is characterized by a fibrotic proliferative inflammatory process encasing the retroperitoneal structures and causing hydronephrosis

**Vesicoureteral reflux**

the most common and serious congenital anomaly.It is a major contributor to renal infection and scarring, Abnormal connections between the bladder and the vagina, rectum, or uterus may create congenital vesicouterine fistulae

**Diverticula**

pouchlike evaginations of the bladder wall that vary from less than 1 cm to 5 to 10 cm in diameter and may be congenital or acquired. The increased intravesical pressure causes *outpouching of the bladder* wall and the formation of diverticula. They are frequently multiple and have narrow necks located between the interweaving hypertrophied muscle bundles

**Exstrophy of the bladder**

a developmental failure in the anterior wall of the abdomen and the bladder, so that the bladder either communicates directly through a large defect with the surface of the body or lies as an opened sac. These lesions are amenable to surgical correction, and longterm survival is possible.

**Urachal anomalies**

The urachus (the canal that connects the fetal bladder with the allantois) is normally obliterated after birth, but it sometimes remains patent in part or in whole. When totally patent, a *fistulous urinary tract* connects the bladder with the umbilicus. In other instances, only the central region of the urachus persists, giving rise to urachal cysts, lined by either urothelium or metaplastic glandular epithelium. *Carcinomas*, mostly glandular tumors, may arise from such cysts

**Urinary tract infections (UTIs)**

typically take the form of nonspecific acute and/or chronic inflammation

1. frequency, which in acute cases may necessitate urination every 15 to 20 minutes
2. lower abdominal pain localized over the bladder region or in the suprapubic region; and
3. dysuria—pain or burning on urination.

**All forms of cystitis are characterized by a triad of symptoms**

**Adenovirus infectio**

* also causes a hemorrhagic cystitis. Persistence of the bacterial infection leads to **chronic cystitis** associated with mononuclear inflammatory infiltrates.

**Follicular cystitis**

* characterized by the presence of lymphoid follicles within the bladder mucosa and underlying wall

**Eosinophilic cystitis**

* manifested by infiltration with submucosal eosinophils, typically is a nonspecific subacute inflammation but may also be a manifestation of a systemic allergic disorder

**Interstitial cystitis**

* a form of chronic cystitis, occurring usually in women. This causes pain and dysuria in the absence of infection. Punctate hemorrhages characterize early lesions, followed classically in late-stage disease by localized ulceration (Hunner ulcer) with inflammation and transmural fibrosis. Mast cells are characteristically seen but are of uncertain

significance

**Malacoplakia**

* occurs in chronic bacterial cystitis
* mostly due to E. coli or Proteus species) and is more common in immunosuppressed patients.


* Lesions are characterized by 3- to 4-cm soft, yellow, mucosal plaques, composed primarily of foamy macrophages stuffed with bacterial debris; the macrophages also display intra-lysosomal laminated calcified concretions called Michaelis Gutmann bodies

**Cystitis glandularis and cystitis cystica**

* These are common lesions of the urinary bladder in which nests of urothelium (*Brunn nests*) grow downward into the lamina propria.
* Here, epithelial cells in the center of the nest undergo metaplasia and take on a cuboidal or columnar appearance (*cystitis glandularis*), or retract to produce cystic spaces lined by flattened urothelium (*cystitis cystica*).
* Because the two processes often coexist, the condition is typically referred to as cystitis cystica et glandularis.
* In a variant of cystitis glandularis goblet cells are present, and the epithelium resembles intestinal mucosa (*intestinal or colonic metaplasia*).

**Squamous metaplasia**

as a response to injury, the urothelium is often replaced by nonkeratinizing squamous epithelium, which is a more durable lining. This should be distinguished from glycogenated squamous epithelium that is normally found in women at the trigone

**Nephrogenic adenoma**

an unusual lesion that results from implantation of shed renal tubular cells at sites of injured urothelium

**Urothelial Tumors**

* run the gamut from small benign lesions to aggressive cancers with a high mortality;
* these can occur anywhere from the renal pelvis to the distal urethra, and many are multifocal at presentation

**Non-invasive papillary tumors**

the most common, with lesions exhibiting a range of atypia that can reflect biologic behavior.

**Carcinoma in situ (CIS)**

represents a high-grade lesion of cytologically malignant cells present within a flat urothelium; the cells often lack cohesiveness and shed into the urine (detectable on urine cytology)

**Exophytic papillomas**

* urothelium over finger-like papillae with loose fibrovascular cores
* have an extremely low incidence of progression or recurrence

**Inverted papillomas**

* bland urothelium extending into the lamina propria
* are uniformly benign.

**Papillary urothelial neoplasms of low malignant potential**

slightly larger than papillomas with thicker urothelium and enlarged nuclei (but rare mitoses) and infrequent invasion

**Low-grade papillary urothelial carcinomas**

characteristically have orderly cytology and architecture, with minimal atypia; they can invade but are rarely fatal lesions

**High-grade papillary urothelial cancers**

* contain discohesive cells with anaplastic features and architectural disarray; these have a high risk (i.e., 80%) for progression and metastases

**Squamous cell carcinomas**

associated with chronic bladder infection and inflammation; these represent 3% to 7% of bladder cancers in the United States, but they occur much more frequently in countries endemic for urinary schistosomiasis

**Mixed urothelial carcinomas with areas of squamous carcinoma**

* invasive, fungating, and/or ulcerating tumors; they are more common than purely squamous cell bladder cancers

**Adenocarcinomas of the bladder**

are rare; they can arise from urachal remnants or in the setting of intestinal metaplasia.

**Mesenchymal Tumors**

* rare
* benign tumors resemble their counterparts elsewhere, with leiomyomas being most common

**Secondary Tumors**

most often by direct extension from primary lesions in nearby organs, cervix, uterus, prostate, and rectum. Lymphomas may involve the bladder as a component of systemic disease, but also, rarely, as primary bladder lymphoma

**Benign Tumor**

rare. The most common is leiomyoma. They all tend to grow as isolated, intramural, encapsulated, oval- tospherical masses, varying in diameter up to several centimeters

**Sarcomas**

* Inflammatory myofibroblastic tumors and various carcinomas may assume sarcomatoid growth patterns and be mistaken histologically for sarcomas.

Urethral Caruncle

* An Inflammatory lesion that presents as a small, red, painful mass about the external urethral meatus, typically in older females
* are exquisitely friable and bleed easily
* Excision is curative

Urethral carcinoma

* Uncommon
* (proximal urethra) are analogous to bladder urothelial malignancy, whereas in the distal urethra, they are more commonly squamous cell carcinomas

Benign Epithelial tumors of Urethra

Include squamous and urothelial papillomas, inverted urothelial papillomas, and condylomas

***Hypospadias and Epispadias***

* 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).
* The abnormal opening is often constricted, resulting in urinary tract obstruction and an increased risk of ascending infections

**Phimosis**

* When the orifice of the prepuce is too small to permit its normal retraction, the condition is designated phimosis.
* Secondary to inflammation
* important bcoz it interferes with cleanliness

and permits the accumulation of secretions

and other debris (smegma)

Balanoposthitis

* non-specific infection by other organisms (e.g., Candida, anaerobic or pyogenic bacteria and Gardnerella)
* Most are a consequence of poor local hygiene in uncircumcised males due to accumulated smegma and can lead to phimosis

**Invasive Squamous Cell Carcinoma**

* associated with poor genital hygiene and high-risk HPV infection.
* more common in populations in which circumcision is not practiced routinely

Condyloma acuminatum

* a benign sexually transmitted wart caused by human papillomavirus (HPV).
* may occur on any moist mucocutaneous surface of the external genitals in either sex. \n

“Low Risk” HPV serotypes

most frequent cause of condylomata acuminata

**Peyronie Disease**

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

Bowen Disease

most commonly affects the penile shaft and scrotum of older men. At these sites, it appears as a solitary, thickened, gray-white, opaque plaque

Bowenoid Papulosis

occurs in sexually active adults; It is distinguished from Bowen disease by the younger age of affected patients and its presentation as multiple (rather than solitary) reddish brown papular lesions.

Invasive Carcinoma

* Most cases occur in men between ages 40 and 70 years
* higher in regions where circumcision is not routinely practiced.
* is related to carcinogens within smegma accumulating under the foreskin, as well as HPV types 16 and 18

Cryptorchidism

* represents failure of descent
* usually unilateral and an isolated anomaly, but it is bilateral in 25% of patients and can occur with other genitourinary malformations
* most cryptorchidism involves abnormalities in the descent through the inguinal canal into the scrotal sac (under the control of androgens)


* undescended testis is palpable in the

inguinal canal

**Nonspecific Epididymitis and Orchitis**

Results from primary urinary tract infection that reaches the epididymis via the vas deferens or spermatic cord lymphatics

Granulomatous (Autoimmune) Orchitis

* presents in middle age as a painless to moderately tender testicular mass of sudden onset
* autoimmune pathogenesis is suspected

Gonorrhea

* Most cases represent retrograde extension of infection from the posterior urethra to the prostate, seminal vesicles, and epididymis
* If untreated, the infection can extend to the testis to produce suppurative orchitis

Mumps

* Mumps orchitis - uncommon in children
* Develops 20% - 30% in postpubertal men infected with mumps
* Acute interstitial orchitis typically develops about 1 week after onset of parotid inflammation

Tuberculosis

* almost always begins in the epididymis, with secondary involvement of the testis
* the histology of caseating granulomas is identical to that seen in other sites

Syphilis

* can occur as both congenital and acquired forms and can present as isolated orchitis without involvement of adnexal structures
* there can be nodular gummas or diffuse interstitial inflammation with edema, lymphoplasmacytic inflammation, and obliterative endarteritis

**Torsion**

* Twisting of the spermatic cord cuts off the testicular venous drainage; since the thick-walled arteries typically remain patent, there is intense vascular engorgement potentially followed by hemorrhagic infarction


* occurs without any inciting injury and can even occur during sleep

Neonatal torsion

occurs either in utero or shortly after birth; it lacks any associated anatomic defect

Adult torsion

typically presents in adolescence as sudden dramatic testicular pain; it is associated with a bilateral anatomic defect giving the testis increased mobility (bell-clapper abnormality)

Lipomas

* commonly involve the proximal spermatic cord
* in some cases, however, fat around the cord only represents retroperitoneal adipose tissue that has been pulled into the inguinal canal with a hernia sac

Adenomatoid tumor \n

* mc benign paratesticular neoplasms ○ small nodules of mesothelial cells
* usually near the upper epididymal pole

Rhabdomyosarcomas

mc in children

Liposarcomas

mc in adults

**Germ cell tumors**

* generally malignant
* Further divided into *seminomas* and *non*

*seminomas*
* Mc malignancy in men between the ages of 15 and 34 years and account for 10% of cancer deaths in that group

Seminoma

* accounts for 50% of all testicular germ cell tumors
* peak incidence between ages 30 and 40 years

Spermatocytic Seminoma

* an uncommon neoplasm


* typically occurring in older patients (older than 65 years)


* usually indolent tumors with little tendency to metastasize; they are not associated with ITGCN

Embryonal Carcinoma

* has a peak incidence between ages 20 and 30 years
* are more aggressive than seminomas

Yolk Sac Tumor (Endodermal Sinus Tumor)

* Mc testicular neoplasm in patients younger than 3 years
* occur as a component of embryonal carcinoma (adult)

Choriocarcinoma

highly malignant neoplasm composed of both cytotrophoblastic and syncytiotrophoblastic elements; it comprises less than 1% of all germ cell tumors

Teratoma

* is a neoplasm showing differentiation along endodermal, mesodermal, and ectodermal lines
* Can occur at any age
* the frequency of teratomas mixed with other germinal cell tumors approaches 50%
* Pure Teratomas are rare

**Leydig Cell tumors**

* occur between the ages of 20 and 60 years
* Tumors can produce androgens, estrogens, and/or corticosteroids


* patients typically present with a testicular mass but can also exhibit changes referable to hormone elaboration

**Sertoli Cell Tumors**

typically present only as a testicular mass and are hormonally silent

**Testicular Lymphoma**

* Mc testicular tumor in patients older than 60 years
* Most are diffuse, large B-cell non- Hodgkin lymphomas and disseminate widely, with a high incidence of central nervous system (CNS) involvement

Hydrocele

Accumulation of serous fluid within the mesothelial lined tunica vaginalis, usually due to generalized edema

Hematocele

Accumulation of blood secondary to trauma, torsion, or a generalized bleeding diathesis

Chylocele

Accumulation of lymphatic fluid secondary to lymphatic obstruction (e.g., elephantiasis)

Spermatocele

Local cystic accumulation of semen in dilated ductuli efferentes or rete testis

Varicocele

Dilated vein in the spermatic cord; may be asymptomatic or contribute to infertility

Malignant mesothelioma

rarely arises in the tunica vaginalis

Acute Bacterial Prostatitis

* Typically caused by organisms associated with UTI


* Prostatic infection occurs through urinary reflux or lymphohematogenous seeding from more distant sites

Chronic Bacterial Prostatitis

* an insidious disorder
* can be asymptomatic or associated with low back pain, suprapubic and perineal discomfort, and dysuria


* frequently associated with a history of recurrent UTI, but WITHOUT previous acute prostatitis; the organisms are those typically involved in acute prostatitis

Chronic Abacterial Prostatitis

* most common form of prostatitis
* Similar manifestations to chronic bacterial prostatitis but WITHOUT recurrent urinary tract infections
* Prostatic secretions contain more than 10 leukocytes per high-power field, but cultures are uniformly negative.

Granulomatous Prostatitis

* the most common cause is related to installation of BCG to treat bladder cancer


* In this setting, prostatic granulomas are of no clinical significance and require no treatment.

Non-specific granulomatous prostatitis

relatively common and represents a reaction to secretions from ruptured prostatic ducts and acini

Benign Prostatic Hyperplasia (BPH)

* AKA Nodular Hyperplasia
* An extremely common disorder caused by 1) periurethral epithelial and 2) stromal hyperplasia that compresses the urethra
* Symptoms are related to urinary flow obstruction

Dihydrotestosterone (DHT)

* Critical mediator in this process
* synthesized by the stromal cells of the prostate from circulating testosterone via the activity of 5a-reductase, type 2.

Adenocarcinoma

* AKA Prostatic Carcinoma
* most common form of cancer in men (29% of U.S. cancers)
* 1 in 6 lifetime risk; it is responsible for 9% of cancer deaths. in men older than 50 years
* Incidence increases in men: from 50’s (20%) → 70’s (70%)
* Uncommon in Asians
* More common in blacks than in whites
* Clinical behavior ranges from aggressively lethal to indolent and incidental.

X-linked AR gene

contains a polymorphic sequence composed of CAG (glutamine) repeats

ARs (shorter glutamine repeats)

* more sensitive to androgens
* Common in African Americans

ARs (more numerous repeats)

* Less sensitive
* Common in Asians

Prostatic intraepithelial neoplasia (PIN)

* the precursor on the spectrum to prostatic carcinoma
* contains many of the molecular changes seen in malignancy

Gleason System

* stratifies prostate cancers into five grades based on their glandular patterns (i.e., 1 1⁄4 closest to normal; 5 1⁄4 no glandular differentiation)
* without regard to cytologic features.
* Low-to moderate-grade Gleason scores - **suggest treatable disease** \n High-grade scores - **grave prognosis.**

**External beam radiotherapy**

can be used to treat prostate cancer that is too locally advanced to be cured by surgery

Prostate Specific Antigen (PSA)

* most important test used in the diagnosis and management of prostate cancer.
* A product of prostatic epithelium
* normally secreted in the semen


* serum levels are elevated to a lesser extent in BPH than prostate cancer, although there is considerable overlap between the two entities.

IMPORTANT POINTS:

* PSA is **organ-specific**, yet **not cancer-**

**specific.**
* Other factors such as BPH, prostatitis, infarct, and instrumentation of the prostate can increase serum PSA levels.
* As men age, their prostates tend to enlarge with BPH, with corresponding higher serum PSA levels.