Lower Urinary Tract and Male Genital System Flashcards
1
Q
What type of epithelium lines the renal pelves, ureters, urinary bladder, and urethra?
A
Urothelium
Urothelium is a special form of transitional epithelium composed of five to six layers of cells.
2
Q
What are the characteristics of urothelium?
A
Urothelium has:
* Oval nuclei
* Linear nuclear grooves
* Large, flattened ‘umbrella cells’ with abundant cytoplasm
These features contribute to its unique function in the urinary tract.
3
Q
What structure supports the urothelium?
A
A well-developed basement membrane
The basement membrane is crucial for the structural integrity of the urothelium.
4
Q
What is the muscularis mucosa?
A
A layer beneath the lamina propria containing wisps of smooth muscle
It is important to differentiate this from the muscularis propria (detrusor muscle) in bladder cancer staging.
5
Q
What happens to bladder musculature when urine flow is obstructed?
A
Hypertrophy of the bladder musculature occurs
This occurs due to increased intravesical pressures.
6
Q
Where do the ureters lie?
A
In a retroperitoneal position
This positioning makes them susceptible to entrapment by retroperitoneal tumors or fibrosis.
7
Q
What condition can occur in middle-aged and older women due to pelvic support relaxation?
A
Cystocele
This condition involves the bladder protruding into the vagina and can lead to difficulty in emptying the bladder.
8
Q
What anatomical structures are located just posterior and inferior to the neck of the bladder in males?
A
Seminal vesicles and prostate
Enlargement of the prostate is a common cause of urinary tract obstruction in older males.
9
Q
What is a common cause of urinary tract obstruction in older males?
A
Enlargement of the prostate
This is often related to benign prostatic hyperplasia.
10
Q
Fill in the blank: The bladder cancers are staged based on the invasion of the ______.
A
muscularis propria
The muscularis propria is also known as the detrusor muscle.
11
Q
What are the layers of the urothelium?
A
Five to six layers of cells
These layers are crucial for the function of the urinary tract.
12
Q
What is the prevalence of congenital anomalies of the ureters?
A
About 2% to 3% of all autopsies
Most congenital anomalies have little clinical significance but certain anomalies may lead to obstruction.
13
Q
What is the most common cause of hydronephrosis in infants and children?
A
Ureteropelvic junction (UPJ) obstruction
UPJ obstruction affects males preferentially and is often associated with other anomalies.
14
Q
In adults, which gender is more commonly affected by UPJ obstruction?
A
Women
UPJ obstruction in adults is most often unilateral.
15
Q
What are common causes of UPJ obstruction?
A
Abnormal organization of smooth muscle bundles, excess stromal deposition of collagen, extrinsic compression
Extrinsic compression can be caused by abnormal renal vessels.
16
Q
What type of tumors are rare in the ureter?
A
Primary tumors
Benign tumors are generally of mesenchymal origin.
17
Q
What is a common tumor-like lesion occurring in children?
A
Fibroepithelial polyp
It is composed of loose, vascularized connective tissue overlaid by urothelium.
18
Q
What is the most frequent primary malignant tumor of the ureter?
A
Urothelial carcinoma
These tumors commonly occur concurrently with urothelial carcinomas of the bladder or renal pelvis.
19
Q
What conditions may arise due to obstructive lesions in the ureters?
A
Hydroureter, hydronephrosis, pyelonephritis
Obstruction can be intrinsic or extrinsic.
20
Q
What is a primary cause of unilateral ureteral obstruction?
A
Proximal intrinsic or extrinsic causes
Examples include stones and neoplasms.
21
Q
What causes bilateral ureteral obstruction?
A
Distal causes
An example is nodular hyperplasia of the prostate.
22
Q
What characterizes sclerosing retroperitoneal fibrosis?
A
Fibrotic proliferative inflammatory process encasing retroperitoneal structures
This condition is more common in males and can cause hydronephrosis.
23
Q
What is IgG4-related disease associated with?
A
Elevated levels of serum immunoglobulin G4 and fibroinflammatory lesions
It can also affect other organs.
24
Q
What are some known etiologies for retroperitoneal fibrosis?
A
- Drug exposures (e.g., ergot derivatives, ß-adrenergic blockers)
- Inflammatory conditions (e.g., vasculitis, Crohn disease)
- Malignancies (e.g., lymphomas, urinary tract carcinomas)
Most cases are considered primary or idiopathic (Ormond disease).
25
What does microscopic examination of sclerosing retroperitoneal fibrosis typically reveal?
Fibrous tissue with lymphocyte infiltrate, plasma cells, eosinophils
## Footnote
Often, plasma cells are IgG4-positive.
26
What is the initial treatment for sclerosing retroperitoneal fibrosis?
Corticosteroids
## Footnote
Many patients may eventually require ureteral stents or surgical intervention.
27
Fill in the blank: The major causes of ureteral obstruction can be classified into intrinsic and _______.
extrinsic
28
What are some intrinsic causes of ureteral obstruction?
* Calculi
* Strictures
* Tumors
* Blood clots
* Neurogenic
## Footnote
Intrinsic causes typically originate from within the ureter.
29
What can cause extrinsic ureteral obstruction?
* Pregnancy
* Periureteral inflammation
* Endometriosis
* Tumors
## Footnote
Extrinsic factors often involve external pressure or inflammation.
30
What is a significant consequence of ureteral obstruction?
It can lead to hydroureter, hydronephrosis, or pyelonephritis, compromising renal function.
31
What is the most common obstructive lesion in children?
Congenital UPJ obstruction.
32
What may cause acute ureteral obstruction in adults?
Obstructing calculi.
33
What are common causes of chronic ureteral obstruction in adults?
Intrinsic or extrinsic tumors, or idiopathic conditions like sclerosing retroperitoneal fibrosis.
34
What is the most common and serious congenital anomaly of the urinary bladder?
Vesicoureteral reflux.
35
What risks are associated with vesicoureteral reflux?
Ascending pyelonephritis and loss of renal function.
36
What are bladder diverticula?
Pouch-like invaginations of the bladder wall, which may be congenital or acquired.
37
What condition is commonly associated with acquired diverticula?
Prostatic hyperplasia.
38
What is exstrophy of the bladder?
A developmental failure in the anterior wall of the abdomen and bladder, leading to direct communication with the abdominal surface.
39
What is the risk associated with exstrophy of the bladder?
Increased risk of adenocarcinoma in the bladder remnant.
40
What is a urachal anomaly?
A condition where the urachal canal remains patent, creating a fistulous connection or cyst.
41
What type of cancer can arise from urachal cysts?
Adenocarcinomas.
42
What are the most common etiologic agents of cystitis?
Coliforms: *Escherichia coli*, *Proteus*, *Klebsiella*, and *Enterobacter*.
43
What predisposing factors are associated with cystitis?
*Bladder calculi*
*Urinary obstruction*
*Diabetes mellitus*
*Instrumentation*
*Immune deficiency*
44
What is acute cystitis characterized by morphologically?
Hyperemia of the mucosa and neutrophilic infiltrate.
45
What may result from persistent bacterial infection in cystitis?
Chronic cystitis associated with mononuclear inflammatory infiltrates.
46
Fill in the blank: Tuberculous cystitis is almost always a sequel to _______.
renal tuberculosis.
47
True or False: Gas-forming bacteria like Clostridium perfringens can lead to emphysematous cystitis.
True.
48
What non-infectious types of cystitis exist?
*Iatrogenic cystitis*
*Follicular cystitis*
*Eosinophilic cystitis*
49
What are cytotoxic agents that may cause hemorrhagic cystitis?
Cyclophosphamide
## Footnote
Hemorrhagic cystitis is a complication associated with certain medications.
50
What are the two types of cystitis that may occur following irradiation of the bladder region?
Acute and chronic radiation cystitis
## Footnote
Radiation can cause damage to the bladder leading to cystitis.
51
What characterizes follicular cystitis?
Presence of lymphoid follicles within the bladder mucosa and underlying wall
## Footnote
Follicular cystitis is a specific morphological form of cystitis.
52
What is eosinophilic cystitis typically a manifestation of?
A systemic allergic disorder
## Footnote
Eosinophilic cystitis is characterized by eosinophil infiltration.
53
What are the three main symptoms of cystitis?
* Frequency
* Lower abdominal pain
* Dysuria
## Footnote
These symptoms can indicate the presence of cystitis.
54
What is a potential serious consequence of cystitis if left untreated?
Pyelonephritis
## Footnote
Cystitis can lead to more severe kidney infections.
55
What underlying disorders are associated with secondary cystitis?
* Prostatic hypertrophy
* Cystocele
* Calculi
* Bladder neoplasms
## Footnote
Addressing these primary lesions is essential for cystitis relief.
56
What is interstitial cystitis commonly defined as?
An unpleasant sensation related to the urinary bladder, with urinary tract symptoms lasting more than six weeks in absence of infection
## Footnote
This condition primarily affects women.
57
What are the characteristic symptoms of interstitial cystitis?
* Severe suprapubic pain
* Urinary frequency
* Urgency
* Hematuria
* Dysuria
## Footnote
Symptoms can vary in intensity and frequency.
58
What are typical cystoscopic findings in interstitial cystitis?
* Mucosal fissures
* Punctate hemorrhages (glomerulations)
## Footnote
These findings help in diagnosing the condition.
59
What is the main role of biopsy in interstitial cystitis?
To rule out carcinoma in situ (CIS)
## Footnote
CIS can present similarly to interstitial cystitis.
60
What is malakoplakia characterized by?
Chronic inflammatory reaction stemming from acquired defects in phagocyte function
## Footnote
It is often associated with chronic bacterial infections.
61
What are the common bacteria associated with malakoplakia?
* E. coli
* Proteus species
## Footnote
Malakoplakia is more frequent in immunocompromised individuals.
62
What does malakoplakia appear as cystoscopically?
Soft yellow, slightly raised mucosal plaques, 3 to 4 cm in diameter
## Footnote
This distinctive appearance aids in diagnosis.
63
What type of cells are abundant in the histology of malakoplakia?
Large foamy macrophages
## Footnote
These macrophages often contain Michaelis-Gutmann bodies.
64
What are Michaelis-Gutmann bodies?
Laminated mineralized concretions resulting from deposition of calcium in enlarged lysosomes
## Footnote
They are typically present within macrophages in malakoplakia.
65
What is polypoid cystitis primarily caused by?
Irritation of the bladder mucosa, often due to instrumentation or indwelling catheters
## Footnote
This form of cystitis is linked to physical trauma to the bladder.
66
What is polypoid cystitis?
A condition characterized by broad bulbous polypoid projections of the urothelium due to marked submucosal edema.
## Footnote
It may be mistaken for papillary urothelial carcinoma both clinically and histologically.
67
What are cystitis glandularis and cystitis cystica?
Common lesions of the urinary bladder where nests of urothelium grow downward into the lamina propria.
## Footnote
Cystitis glandularis features cuboidal or columnar epithelial cells, while cystitis cystica produces cystic spaces lined by flattened urothelium.
68
What is cystitis cystica et glandularis?
A condition that refers to the coexistence of cystitis cystica and cystitis glandularis.
## Footnote
It is characterized by nests of urothelium and the presence of goblet cells resembling intestinal mucosa.
69
What is intestinal or colonic metaplasia?
A variant of cystitis glandularis where the epithelium resembles intestinal mucosa.
## Footnote
Extensive intestinal metaplasia can be a precursor to adenocarcinoma.
70
What occurs in squamous metaplasia of the bladder?
The urothelium is replaced by nonkeratinizing or keratinizing squamous epithelium as a response to chronic injury.
## Footnote
This can be a precursor to dysplastic lesions and squamous cell carcinoma.
71
What is nephrogenic adenoma?
An unusual lesion that may not be a form of true metaplasia, often caused by implantation and growth of renal tubular cells.
## Footnote
It can mimic malignant lesions microscopically and may produce symptoms raising suspicion of cancer.
72
What are common symptoms of bladder inflammatory lesions?
Frequency and dysuria.
## Footnote
Acute or chronic bacterial cystitis is particularly common in women.
73
What is the most common cause of acute bacterial cystitis?
Retrograde spread of colonic bacteria.
## Footnote
Other cystitis forms can have iatrogenic causes, such as radiation cystitis.
74
What percentage of bladder tumors are of epithelial origin?
>95%.
## Footnote
Urothelial neoplasms are the most common type, followed by squamous and glandular neoplasms.
75
What percentage of bladder tumors are urothelial neoplasms?
About 90%.
## Footnote
They can range from benign lesions to aggressive cancers.
76
What are the two distinct precursor lesions to invasive urothelial carcinoma?
Noninvasive papillary tumors and flat noninvasive urothelial carcinoma in situ (CIS).
77
List some types of tumors of the urinary bladder.
* Noninvasive urothelial tumors
* Infiltrating urothelial carcinoma
* Adenocarcinoma
* Squamous cell carcinoma
* Mixed carcinoma
* Small-cell carcinoma
* Sarcomas
* Papilloma
* Invasive papillary carcinoma
* Flat noninvasive carcinoma (CIS)
* Flat invasive carcinoma
78
True or False: Bladder cancer is the fourth most common cancer in American men.
True.
79
Fill in the blank: Extensive multifocal keratinizing squamous metaplasia is a precursor to _______.
[dysplastic lesions and in situ and invasive squamous cell carcinoma].
80
What are papillary tumors and what do they originate from?
Papillary tumors originate from papillary urothelial hyperplasia.
81
What is Schistosoma haematobium and its association with bladder cancer?
Schistosoma haematobium infections are an established risk factor for bladder cancer, particularly in endemic areas like Egypt and Sudan.
82
What is carcinoma in situ (CIS)?
CIS is a term used to describe epithelial lesions that have the cytologic features of malignancy but are confined to the epithelium without basement membrane invasion.
83
What percentage of bladder cancers are squamous cell carcinomas?
Seventy percent of bladder cancers are squamous cell carcinomas.
84
What is the significance of precursor lesions in invasive bladder cancer?
In about one-half of individuals with invasive bladder cancer, precursor lesions are not detected because they may have been destroyed by the invasive component.
85
How does invasion into the muscularis propria affect bladder cancer prognosis?
Invasion into the muscularis propria is associated with a 30% 5-year mortality rate.
86
What demographic factors influence the incidence of bladder cancer?
The incidence is higher in men (3:1 male-to-female ratio), higher income nations, and urban dwellers.
87
What is the age range of most bladder cancer patients?
About 80% of patients are between 50 and 80 years of age.
88
What is the most important risk factor for urothelial carcinoma?
Cigarette smoking is the most important influence, increasing risk threefold to sevenfold.
89
Fill in the blank: Between ______% and ______% of all bladder cancers among men are associated with cigarette use.
50% and 80%
90
What are some chemical carcinogens implicated in bladder cancer?
Aryl amines, particularly 2-naphthylamine and related compounds.
91
What genetic alterations are commonly found in muscle-invasive bladder cancers?
Gains-of-function alterations in growth factor receptor pathways, amplifications of FGFR, and mutations in RAS and PI 3-kinase.
92
What mutations are prevalent in all muscle-invasive bladder cancers?
Mutations that disrupt the function of TP53 and RB.
93
True or False: Bladder cancer has a low burden of somatic mutations compared to other carcinogen-induced cancers.
False
94
What is the relationship between environmental exposures and bladder cancer?
Environmental exposures, including chemicals and smoking, are significant risk factors for bladder cancer.
95
What is the typical progression pathway from carcinoma in situ to invasive cancer?
CIS progresses to invasive cancer through additional genetic and epigenetic changes.
96
What are oncogenes and tumor suppressor genes involved in?
Cell cycle regulation, chromatin regulation, DNA repair, and growth factor signaling pathways
97
What does RNA expression analysis suggest about urothelial tumors?
The existence of several relatively distinct molecular subtypes
98
What is the grading system of urothelial tumors used for?
To classify the appearance and severity of urothelial tumors
99
What percentage of bladder tumors do papillomas represent?
1% or less
100
Describe the morphology of papillary lesions.
Red, elevated excrescences ranging from less than 1 cm to large masses up to 5 cm in diameter
101
What are exophytic papillomas?
Small (0.5 to 2 cm), delicate structures superficially attached to the mucosa by a stalk
102
What histological characteristics do the individual finger-like papillae of papillomas have?
A central core of loose fibrovascular tissue covered by epithelium identical to normal urothelium
103
What is the recurrence and progression rate for papillomas?
Rare
104
What does PUNLMP stand for?
Papillary Urothelial Neoplasms of Low Malignant Potential
105
How does low-grade papillary urothelial carcinoma appear histologically?
Overall orderly appearance with scattered hyperchromatic nuclei and mitotic figures
106
What characterizes high-grade papillary urothelial carcinoma?
Marked cytologic atypia
107
What are inverted papillomas?
Completely benign lesions consisting of inter-anastomosing cords of cytologically bland urothelium that extend down into the lamina propria
## Footnote
They simulate an invasive process.
108
What differentiates papillary urothelial neoplasms of low malignant potential (PUNLMP) from papillomas?
Thicker urothelium with greater density of cells
## Footnote
At cystoscopy, these tumors tend to be larger than papillomas.
109
What is the typical architectural appearance of low-grade papillary urothelial carcinomas?
Orderly architectural appearance and low-grade cytologic atypia
## Footnote
Cells are evenly spaced and cohesive.
110
What features characterize high-grade papillary urothelial carcinomas?
Dyscohesive cells, large hyperchromatic nuclei, irregular nuclear chromatin, and prominent nucleoli
## Footnote
Frequent mitotic figures, including atypical ones.
111
What is carcinoma in situ (CIS) defined by?
Presence of cytologically malignant cells within a flat urothelium
## Footnote
May range from full-thickness cytologic atypia to scattered malignant cells.
112
What is a common feature shared between CIS and high-grade papillary urothelial carcinoma?
Lack of cohesiveness, leading to shedding of malignant cells into the urine
## Footnote
Extensive shedding may leave only a few CIS cells clinging to the basement membrane.
113
What is the prognosis for untreated CIS?
50% to 75% of CIS progresses to invasive cancer
## Footnote
Early detection and treatment are crucial.
114
What is the most important prognostic factor for invasive urothelial carcinoma?
Extent of spread (stage) based primarily on depth of invasion in the bladder wall
## Footnote
Determines treatment modality.
115
What treatment is indicated for invasion of the muscularis propria layer?
Radical cystectomy or radiation therapy with neoadjuvant or adjuvant chemotherapy
## Footnote
Treatment decisions are influenced by cancer staging.
116
True or False: Low-grade papillary urothelial carcinomas have a high rate of progression to muscle-invasive bladder cancer.
False
## Footnote
They have a much lower incidence of progression compared to high-grade lesions.
117
Fill in the blank: CIS may appear as an area of mucosal ______, granularity, or thickening without an evident intraluminal mass.
reddening
## Footnote
CIS is commonly multifocal and may involve the bladder surface.
118
What are inverted papillomas?
Completely benign lesions consisting of inter-anastomosing cords of cytologically bland urothelium that extend down into the lamina propria
## Footnote
They simulate an invasive process.
119
What differentiates papillary urothelial neoplasms of low malignant potential (PUNLMP) from papillomas?
Thicker urothelium with greater density of cells
## Footnote
At cystoscopy, these tumors tend to be larger than papillomas.
120
What is the typical architectural appearance of low-grade papillary urothelial carcinomas?
Orderly architectural appearance and low-grade cytologic atypia
## Footnote
Cells are evenly spaced and cohesive.
121
What features characterize high-grade papillary urothelial carcinomas?
Dyscohesive cells, large hyperchromatic nuclei, irregular nuclear chromatin, and prominent nucleoli
## Footnote
Frequent mitotic figures, including atypical ones.
122
What is carcinoma in situ (CIS) defined by?
Presence of cytologically malignant cells within a flat urothelium
## Footnote
May range from full-thickness cytologic atypia to scattered malignant cells.
123
What is a common feature shared between CIS and high-grade papillary urothelial carcinoma?
Lack of cohesiveness, leading to shedding of malignant cells into the urine
## Footnote
Extensive shedding may leave only a few CIS cells clinging to the basement membrane.
124
What is the prognosis for untreated CIS?
50% to 75% of CIS progresses to invasive cancer
## Footnote
Early detection and treatment are crucial.
125
What is the most important prognostic factor for invasive urothelial carcinoma?
Extent of spread (stage) based primarily on depth of invasion in the bladder wall
## Footnote
Determines treatment modality.
126
What treatment is indicated for invasion of the muscularis propria layer?
Radical cystectomy or radiation therapy with neoadjuvant or adjuvant chemotherapy
## Footnote
Treatment decisions are influenced by cancer staging.
127
True or False: Low-grade papillary urothelial carcinomas have a high rate of progression to muscle-invasive bladder cancer.
False
## Footnote
They have a much lower incidence of progression compared to high-grade lesions.
128
Fill in the blank: CIS may appear as an area of mucosal ______, granularity, or thickening without an evident intraluminal mass.
reddening
## Footnote
CIS is commonly multifocal and may involve the bladder surface.
129
What are the WHO/ISUP Grades for flat lesions in urothelial tumors?
• Urothelial proliferation of uncertain malignant potential (flat hyperplasia)
• Urothelial dysplasia
• Urothelial dysplasia in situ
## Footnote
These classifications help in determining the malignant potential of flat lesions.
130
Name the types of exophytic papillary lesions in urothelial tumors.
• 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
## Footnote
These lesions vary in their malignant potential and are important in grading bladder cancer.
131
What is the most common symptom of bladder cancer?
Painless hematuria
## Footnote
Other symptoms may include frequency, urgency, and dysuria.
132
What are the potential complications of obstruction of the ureteral orifice in bladder cancer?
• Pyelonephritis
• Hydronephrosis
## Footnote
These conditions can arise due to blockage caused by tumors.
133
What factors influence the treatment and course of bladder carcinoma?
Tumor grade and stage
## Footnote
The key variable is whether the tumor is muscle-invasive or not.
134
What percentage of urothelial neoplasms are non-muscle-invasive?
70% to 80%
## Footnote
This category includes noninvasive papillary urothelial tumors and those that invade only the lamina propria.
135
What is the initial treatment for small, localized low-grade papillary tumors?
Diagnostic transurethral resection
## Footnote
This procedure is typically sufficient for small and localized tumors.
136
What treatment is used for high-grade multifocal tumors or those associated with lamina propria invasion?
Intravesical instillation of bacillus Calmette-Guérin (BCG)
## Footnote
BCG elicits a local inflammatory reaction that can destroy the tumor.
137
What is the recurrence rate for non-muscle-invasive bladder cancers?
Up to 70%
## Footnote
This high tendency for recurrence necessitates ongoing surveillance.
138
What factors are related to the risk of recurrence and progression in bladder cancer?
• Tumor size
• Stage
• Grade
• Multifocality
• Prior recurrence
• Presence of CIS in surrounding mucosa
## Footnote
Each of these factors contributes to the likelihood of tumor return or advancement.
139
What is the 10-year survival rate for papillomas, PUNLMP, and low-grade papillary urothelial cancer?
98%
## Footnote
This statistic holds true regardless of the number of recurrences.
140
What percentage of high-grade papillary urothelial carcinomas lead to death?
About 25%
## Footnote
This highlights the aggressive nature of high-grade tumors.
141
What is the likelihood of progression to muscle-invasive cancer for patients with CIS only?
28%
## Footnote
This is in contrast to 59% for those with CIS associated with infiltrating urothelial carcinoma.
142
What is the annual burden on healthcare resources imposed by bladder cancer in the United States?
Over 3 billion dollars
## Footnote
This figure reflects the extensive monitoring and treatment needs for bladder cancer patients.
143
What is the treatment for muscle-invasive bladder carcinoma?
Radical cystectomy or cystoprostatectomy, or radiation therapy with neoadjuvant and/or adjuvant chemotherapy
## Footnote
These treatments are necessary for managing more advanced stages of bladder cancer.
144
What does the pTNM classification system assess in urinary bladder carcinoma?
Tumor size, lymph node involvement, and metastasis
## Footnote
This system is crucial for staging bladder cancer.
145
What does pTX indicate in the pTNM classification?
Primary tumor cannot be assessed
## Footnote
This classification is used when the tumor's status is unclear.
146
What does Tis stand for in the pTNM classification?
Urothelial carcinoma in situ: 'flat tumor'
## Footnote
Tis indicates a non-invasive form of cancer.
147
What is the most common bladder sarcoma in adults?
Leiomyosarcoma
## Footnote
This type of sarcoma is notable in bladder cancer cases.
148
What is the primary treatment for muscle-invasive bladder cancer?
Radical cystectomy
## Footnote
Indicated in cases of CIS or high-grade papillary cancer refractory to BCG, CIS extending into prostatic urethra, and non-muscle-invasive high-grade carcinoma that is too extensive.
149
What is the 5-year survival rate for most metastatic bladder tumors responding to chemotherapy?
15%
## Footnote
Most metastatic tumors respond poorly to chemotherapy.
150
What percentage of metastatic bladder carcinomas respond to immune checkpoint inhibitors?
30%
## Footnote
This subset may respond dramatically, providing hope for patients.
151
What type of carcinoma makes up 3% to 7% of bladder cancers in the United States?
Squamous cell carcinoma
## Footnote
More frequent in countries where urinary schistosomiasis is endemic.
152
From what does pure squamous cell carcinoma arise?
Atypical keratinizing mucosa
## Footnote
Associated with chronic bladder irritation and infection.
153
What is the most common benign tumor in the bladder?
Leiomyoma
## Footnote
Typically grows as isolated, intramural, encapsulated masses.
154
What is the most common bladder sarcoma in infants or children?
Embryonal rhabdomyosarcoma
## Footnote
May manifest as a polypoid grape-like mass (sarcoma botryoides).
155
What is the most common bladder sarcoma in adults?
Leiomyosarcoma
## Footnote
Discussed in Chapter 26.
156
What is the most common cause of bladder outlet obstruction in males?
Enlargement of the prostate gland due to benign prostatic hyperplasia (BPH)
## Footnote
Less common in females, often caused by cystocele.
157
List some causes of bladder obstruction.
* Congenital urethral strictures
* Inflammatory urethral strictures
* Inflammatory fibrosis and contraction of the bladder
* Bladder tumors
* Invasion of the bladder neck by tumors
* Mechanical obstructions
* Injury of nerves controlling bladder contraction
## Footnote
These conditions can lead to significant clinical issues.
158
What morphological change occurs in the bladder wall during early obstruction?
Thickening of the bladder wall
## Footnote
Due to smooth muscle hypertrophy.
159
What happens to the bladder wall in cases of acute obstruction or terminal disease?
The bladder may become extremely dilated
## Footnote
May reach the brim of the pelvis or umbilicus, with a markedly thinned wall.
160
True or False: Non-muscle-invasive bladder cancer rarely recurs.
False
## Footnote
Non-muscle-invasive bladder cancer frequently recurs but rarely progresses in stage or grade.
161
What are the key tumor suppressor genes associated with muscle-invasive bladder cancers?
TP53 and RB
## Footnote
These genes are often inactivated in muscle-invasive cancers.
162
What is the clinical significance of molecular subtyping in bladder cancer?
Identifies several molecular subtypes for prognostic and potential therapeutic significance
## Footnote
This is an area of ongoing evaluation.
163
What is urethritis divided into?
Gonococcal and non-gonococcal causes
164
What organism is responsible for 25% to 60% of nongonococcal urethritis in men?
Chlamydia (e.g., Chlamydia trachomatis)
165
What is a common cause of nongonococcal urethritis in women?
Mycoplasma (Ureaplasma urealyticum)
166
What conditions can accompany urethritis in women?
Cystitis
167
What conditions can accompany urethritis in men?
Prostatitis
168
What is reactive arthritis associated with?
The clinical triad of arthritis, conjunctivitis, and urethritis
169
What are the typical morphologic changes in urethritis?
Typical of inflammation in other sites within the urinary tract
170
What is a urethral caruncle?
An inflammatory lesion presenting as a small, red, painful mass at the external urethral meatus
171
In which demographic is urethral caruncle typically found?
Older females
172
What are benign epithelial tumors of the urethra?
* Squamous papillomas
* Urothelial papillomas
* Inverted urothelial papillomas
* Condylomas
173
What type of carcinoma is uncommon in the urethra?
Primary carcinoma
174
What type of cancer arises from the proximal urethra?
Urothelial differentiation cancers, analogous to bladder cancers
175
What type of cancer is more common in the distal urethra?
Squamous cell carcinomas and HPV-related lesions
176
What congenital anomaly involves an abnormal opening on the ventral surface of the penis?
Hypospadias
177
What congenital anomaly involves an abnormal opening on the dorsal surface of the penis?
Epispadias
178
What is the incidence of hypospadias in live male births?
Approximately 1 in 300
179
What condition is characterized by an abnormally small prepuce opening?
Phimosis
180
What are potential complications of phimosis?
* Interference with cleanliness
* Accumulation of secretions
* Secondary infections
* Increased risk for penile carcinoma
181
What does balanoposthitis refer to?
Infection of the glans and prepuce
182
What are common agents causing balanoposthitis?
* C. albicans
* Anaerobic bacteria
183
What are common agents causing infections in uncircumcised males?
C. albicans, anaerobic bacteria, Gardnerella, and pyogenic bacteria
## Footnote
These infections often result from poor local hygiene and the accumulation of smegma.
184
What is smegma?
Accumulation of desquamated epithelial cells, sweat, and debris
## Footnote
It acts as a local irritant and can lead to inflammatory scarring and phimosis.
185
What types of tumors are most common in the penis?
Squamous cell carcinoma and benign genital warts (condyloma acuminatum)
## Footnote
Tumors of the penis are considered uncommon overall.
186
What causes condyloma acuminatum?
Human papillomavirus (HPV)
## Footnote
It is a benign sexually transmitted wart that may occur on any moist mucocutaneous surface.
187
Which HPV serotypes are most frequently associated with condyloma acuminatum?
HPV 6 and HPV 11
## Footnote
These are classified as 'low-risk' HPV serotypes.
188
Where do penile lesions of condyloma acuminatum typically occur?
Coronal sulcus and inner surface of the prepuce
## Footnote
They can present as single or multiple red papillary excrescences.
189
What histological features are characteristic of condyloma acuminatum?
Branching, villous, papillary connective tissue stroma covered by epithelium
## Footnote
Features include superficial hyperkeratosis and acanthosis.
190
What is Peyronie disease characterized by?
Hard penile plaques resulting from collagen deposition in connective tissue
## Footnote
It leads to penile curvature and pain during intercourse.
191
What is the believed cause of the fibrosis in Peyronie disease?
Microvascular trauma and subsequent organizing sclerosing chronic inflammation
## Footnote
This condition is considered reactive rather than neoplastic.
192
What is penile intraepithelial neoplasia (PeIN)?
Squamous lesions confined to the epidermis by an intact basement membrane
## Footnote
It includes in situ squamous lesions and may be HPV-related or non-HPV-related.
193
What are the two types of penile intraepithelial neoplasia (PeIN)?
* HPV-related (undifferentiated)
* Non-HPV-related (differentiated)
## Footnote
Differentiated PeIN is associated with balanitis xerotica obliterans.
194
What is Bowen disease?
A carcinoma in situ of the penis characterized by hyperchromatic, dysplastic dyskeratotic epithelial cells and scattered mitoses.
195
What factors contribute to non-HPV-related penile cancer?
Poor hygiene and chronic inflammation.
196
How can HPV vaccines impact penile cancer?
They may help reduce the incidence of penile cancer and condyloma acuminatum.
197
What are other risk factors for penile cancer?
Cigarette smoking and chronic inflammatory conditions such as lichen sclerosis et atrophicus.
198
What is the role of high-risk HPV in penile carcinoma?
It encodes E6 and E7 proteins that inactivate p53 and RB tumor suppressor proteins, leading to genomic instability and increased proliferation.
199
What does the E6 protein do?
Stimulates telomerase expression, leading to cellular immortalization.
200
What is the significance of the E7 protein?
Induces feedback loops that increase levels of the cyclin-dependent kinase inhibitor p16.
201
What is the clinical manifestation of Bowen disease?
Appears as a solitary, thickened, gray-white, opaque plaque, or a velvety red appearance when affecting the glans.
202
What histological features are seen in Bowen disease?
Dysplastic squamous cells with large hyperchromatic irregular nuclei and numerous atypical mitoses.
203
What percentage of Bowen disease cases progress to infiltrating squamous cell carcinoma?
10%.
204
What characterizes Bowenoid papulosis?
Multiple reddish brown papular lesions in sexually active adults, usually regressing spontaneously.
205
What is the demographic most affected by invasive squamous cell carcinoma of the penis?
Middle-aged and older patients (ages 40 to 70).
206
What percentage of cancers in males does penile carcinoma account for in the United States?
Less than 1%.
207
What are some socio-economic factors associated with penile cancer?
Low income status and poor hygiene habits.
208
How does circumcision affect the risk of penile cancer?
It confers protection and is associated with lower incidence rates.
209
Where do squamous cell carcinomas of the penis typically originate?
In the glans or inner surface of the prepuce near the coronal sulcus.
210
What are the macroscopic appearances of penile tumors?
Irregular, fungating masses; flat, indurated lesions; or large verruciform/papillary tumors.
211
What does the WHO 2016 classification of penile squamous cell carcinoma recognize?
HPV-related and non-HPV-related categories, each with different histologies.
212
What is the most common type of penile squamous cell carcinoma?
Conventional (usual) squamous cell carcinoma.
213
What are the prognostic factors in penile carcinoma?
Stage, grade, histologic subtype, vascular invasion, and perineural invasion.
214
Which histologic subtype of penile carcinoma is well differentiated?
Verrucous and papillary carcinomas (grade I tumors).
215
Which histologic subtype of penile carcinoma is poorly differentiated?
Sarcomatoid and basaloid carcinomas (grade 3 tumors).
216
What is verrucous carcinoma?
An exophytic, warty well-differentiated, non-HPV-related variant that invades.
217
What are the types of non-HPV-related squamous cell carcinoma of the penis?
* Squamous cell carcinoma, usual type
* Pseudohyperplastic carcinoma
* Pseudoglandular carcinoma
* Verrucous carcinoma
* Carcinoma cuniculatum
* Papillary squamous cell carcinoma
* Adenosquamous carcinoma
* Sarcomatoid (spindle cell) carcinoma
* Mixed squamous cell carcinoma
## Footnote
These classifications are based on the World Health Organization 2016 Pathologic Classification of Squamous Cell Carcinoma of the Penis.
218
What are the types of HPV-related squamous cell carcinoma of the penis?
* Basaloid squamous cell carcinoma
* Papillary-basaloid carcinoma
* Warty carcinoma
* Warty-basaloid carcinoma
* Clear cell squamous carcinoma
* Lymphoepithelioma-like carcinoma
## Footnote
These classifications are based on the World Health Organization 2016 Pathologic Classification of Squamous Cell Carcinoma of the Penis.
219
What are the two pathogenic pathways related to squamous cell carcinoma of the penis?
One related to HPV and the other unrelated to HPV.
220
Where does squamous cell carcinoma of the penis typically occur?
On the glans or shaft of the penis.
221
What is the clinical feature of invasive squamous cell carcinoma of the penis?
Lesions are nonpainful until they undergo secondary ulceration and infection.
222
What is the prognosis for patients with penile cancer metastasis to multiple, bilateral lymph nodes?
Guarded prognosis with reported 5-year disease-specific survival rates ranging from 7% to 60%.
223
What are common congenital abnormalities associated with the position of the urethra?
* Epispadias
* Hypospadias
## Footnote
These conditions are characterized by abnormal positioning of the urethra.
224
What is cryptorchidism?
A complete or partial failure of the intra-abdominal testes to descend into the scrotal sac.
225
What is the incidence of cryptorchidism in 1-year-old boys?
Approximately 1%.
226
What are the two phases of testicular descent?
* Transabdominal phase
* Inguinoscrotal phase
227
What hormone controls the transabdominal phase of testicular descent?
Müllerian-inhibiting substance.
228
What mediates the inguinoscrotal phase of testicular descent?
Androgen-induced release of calcitonin gene-related peptide from the genitofemoral nerve.
229
What is the most common site for the arrest of testicular descent?
Inguinal canal.
230
What histologic changes occur in cryptorchid testes?
* Thickening of the basement membrane of the spermatic tubules
* Loss of spermatogonia
* Dense cords of hyaline connective tissue
* Prominent Leydig cells
## Footnote
These changes begin as early as 2 years of age.
231
What percentage of patients with cryptorchidism have bilateral involvement?
25%.
232
True or False: Cryptorchidism is often associated with a well-defined hormonal disorder.
False.
233
What is cryptorchidism?
Incomplete descent of the testis from the abdomen to the scrotum
## Footnote
Present in about 1% of 1-year-old male infants.
234
What are the associated risks of cryptorchidism?
* Tubular atrophy
* Sterility
* Increased risk for testicular cancer (three- to fivefold)
## Footnote
Orchiopexy reduces but does not completely eliminate these risks.
235
What is the recommended age for performing orchiopexy?
6 to 12 months of age
## Footnote
This is to prevent development of histologic changes.
236
What percentage of patients may still have deficient spermatogenesis after orchiopexy?
10% to 60%
## Footnote
Even after surgical correction, spermatogenesis may remain deficient.
237
What conditions can cause testicular atrophy?
* Atherosclerotic narrowing
* Inflammatory orchitis
* Cryptorchidism
* Hypopituitarism
* Malnutrition
* Irradiation
* Antiandrogens
* Cirrhosis
* Genetic failure (e.g., Klinefelter syndrome)
* Exhaustion atrophy
## Footnote
These conditions lead to gross and microscopic alterations in the testes.
238
True or False: Inflammatory disorders are more common in the epididymis than the testis.
True
## Footnote
Conditions like tuberculosis and gonorrhea primarily affect the epididymis.
239
What are common pathogens associated with epididymitis in sexually active men under 35?
* C. trachomatis
* Neisseria gonorrhoeae
## Footnote
These are sexually transmitted pathogens.
240
What are common pathogens associated with epididymitis in men over 35?
* E. coli
* Pseudomonas
## Footnote
These are common urinary tract pathogens.
241
What are the morphological characteristics of bacterial infection in the epididymis?
* Acute inflammation
* Congestion
* Edema
* Neutrophil infiltration
## Footnote
Infection usually starts in interstitial connective tissue and can extend to tubules.
242
Fill in the blank: The testicular atrophy that occurs due to cryptorchidism may lead to _______.
[sterility]
243
What is the primary concern associated with undescended testis in cryptorchidism?
Increased risk for germ cell neoplasm
## Footnote
This is believed to be linked to an in utero defect in gonadal cell development.
244
What is cryptorchidism?
Incomplete descent of the testis from the abdomen to the scrotum
## Footnote
Present in about 1% of 1-year-old male infants.
245
What are the associated risks of cryptorchidism?
* Tubular atrophy
* Sterility
* Increased risk for testicular cancer (three- to fivefold)
## Footnote
Orchiopexy reduces but does not completely eliminate these risks.
246
What is the recommended age for performing orchiopexy?
6 to 12 months of age
## Footnote
This is to prevent development of histologic changes.
247
What percentage of patients may still have deficient spermatogenesis after orchiopexy?
10% to 60%
## Footnote
Even after surgical correction, spermatogenesis may remain deficient.
248
What conditions can cause testicular atrophy?
* Atherosclerotic narrowing
* Inflammatory orchitis
* Cryptorchidism
* Hypopituitarism
* Malnutrition
* Irradiation
* Antiandrogens
* Cirrhosis
* Genetic failure (e.g., Klinefelter syndrome)
* Exhaustion atrophy
## Footnote
These conditions lead to gross and microscopic alterations in the testes.
249
True or False: Inflammatory disorders are more common in the epididymis than the testis.
True
## Footnote
Conditions like tuberculosis and gonorrhea primarily affect the epididymis.
250
What are common pathogens associated with epididymitis in sexually active men under 35?
* C. trachomatis
* Neisseria gonorrhoeae
## Footnote
These are sexually transmitted pathogens.
251
What are common pathogens associated with epididymitis in men over 35?
* E. coli
* Pseudomonas
## Footnote
These are common urinary tract pathogens.
252
What are the morphological characteristics of bacterial infection in the epididymis?
* Acute inflammation
* Congestion
* Edema
* Neutrophil infiltration
## Footnote
Infection usually starts in interstitial connective tissue and can extend to tubules.
253
Fill in the blank: The testicular atrophy that occurs due to cryptorchidism may lead to _______.
[sterility]
254
What is the primary concern associated with undescended testis in cryptorchidism?
Increased risk for germ cell neoplasm
## Footnote
This is believed to be linked to an in utero defect in gonadal cell development.
255
What is the consequence of inflammation of the epididymis and testis?
Fibrous scarring, which may produce sterility
## Footnote
Leydig cells are usually not destroyed, so androgen production remains relatively unaffected.
256
What is idiopathic granulomatous orchitis characterized by histologically?
Granulomas restricted to spermatic tubules
## Footnote
It may present as a moderately tender or painless testicular mass.
257
What is a frequent complication of neglected gonococcal infection?
Extension of infection to the prostate, seminal vesicles, and epididymis
## Footnote
This may lead to epididymal abscesses and extensive destruction.
258
What percentage of postpubertal males experience orchitis due to mumps?
20% to 30%
## Footnote
Orchitis typically develops one week after parotid gland swelling.
259
Where does tuberculosis typically begin when it involves the male genital tract?
In the epididymis
## Footnote
From there, it may spread to the testis.
260
What are the two morphologic patterns of reaction in syphilis affecting the testis?
1. Obliterative endarteritis with peri-vascular cuffs
2. Granulomatous inflammation (gumma)
## Footnote
The testis is almost invariably involved first in both acquired and congenital syphilis.
261
What are some rare causes of orchitis?
* Leprosy
* Sarcoidosis
* Crohn disease
* Malakoplakia
* Toxoplasmosis
* Tungi
* Parasites
* Brucellosis
## Footnote
These conditions may also affect the male genital tract.
262
What occurs during testicular torsion?
Twisting of the spermatic cord cuts off venous drainage
## Footnote
This can lead to testicular infarction and is considered a true urologic emergency.
263
What are the two settings in which testicular torsion occurs?
* Neonatal torsion
* Adult torsion
## Footnote
Neonatal torsion occurs in utero or shortly after birth, while adult torsion typically occurs in adolescence.
264
What is the recommended action if the testis is manually untwisted within 6 hours of torsion onset?
The affected testis may be spared an orchiectomy
## Footnote
If untreated, torsion frequently leads to testicular infarction.
265
What anatomical defect is associated with adult testicular torsion?
Bilateral anatomic defect leading to increased mobility of the testes (bell-clapper abnormality)
## Footnote
This can result in the need for contralateral orchidopexy to prevent recurrence.
266
What morphologic changes occur depending on the duration of testicular torsion?
* Intense congestion
* Widespread hemorrhage
* Testicular infarction
## Footnote
In advanced stages, the testis may consist entirely of necrotic, hemorrhagic tissue.
267
Where do infections in the male reproductive system invariably begin?
Epididymis
## Footnote
Infections can spread to the testis from the epididymis.
268
What is the most common benign paratesticular tumor?
Adenomatoid tumor
## Footnote
Adenomatoid tumors are mesothelial in nature and typically occur near the upper pole of the epididymis.
269
What are the common malignant paratesticular tumors in children and adults?
Children: Rhabdomyosarcomas, Adults: Liposarcomas
## Footnote
These tumors are the most frequently observed malignant paratesticular tumors.
270
What percentage of testicular neoplasms are germ cell tumors (GCTs)?
95%
## Footnote
GCTs are responsible for the overwhelming majority of testicular lesions.
271
What is the classification of noninvasive germ cell neoplasia?
Germ cell neoplasia in situ
## Footnote
This is a precursor to invasive germ cell tumors.
272
List some types of nonseminomatous germ cell tumors.
* Embryonal carcinoma
* Yolk sac tumor, postpubertal type
* Choriocarcinoma
* Teratoma, postpubertal type
* Teratoma with somatic-type malignancy
## Footnote
These tumors are classified as nonseminomatous germ cell tumors.
273
What is the lifetime risk of developing germ cell tumors highest?
Northern Europe and New Zealand
## Footnote
The lowest risk is observed in Africa and Asia.
274
What was the predicted number of new cases of germ cell tumors in the United States in 2019?
9560 new cases
## Footnote
There were also predicted 410 deaths from germ cell tumors in the same year.
275
What are some environmental factors contributing to germ cell tumor development?
* Cryptorchidism
* Environmental exposures
* Population migration studies
## Footnote
These factors suggest a link between environmental influences and the incidence of germ cell tumors.
276
What genetic factors are associated with germ cell tumor development?
* Germline variants in KIT, BAK
* KIT mutation
* Isochromosome 12p
## Footnote
These genetic factors contribute to the pathogenesis of germ cell tumors.
277
True or False: Testicular germ cell tumors predominantly affect males older than 45 years.
False
## Footnote
GCTs commonly affect Caucasian males between 15 and 45 years of age.
278
Fill in the blank: The most common benign tumor that occurs near the testis is the _______.
Adenomatoid tumor
## Footnote
This tumor can be identified intraoperatively, potentially sparing the patient from orchiectomy.
279
Where do infections in the male reproductive system invariably begin?
Epididymis
## Footnote
Infections can spread to the testis from the epididymis.
280
What is the most common benign paratesticular tumor?
Adenomatoid tumor
## Footnote
Adenomatoid tumors are mesothelial in nature and typically occur near the upper pole of the epididymis.
281
What are the common malignant paratesticular tumors in children and adults?
Children: Rhabdomyosarcomas, Adults: Liposarcomas
## Footnote
These tumors are the most frequently observed malignant paratesticular tumors.
282
What percentage of testicular neoplasms are germ cell tumors (GCTs)?
95%
## Footnote
GCTs are responsible for the overwhelming majority of testicular lesions.
283
What is the classification of noninvasive germ cell neoplasia?
Germ cell neoplasia in situ
## Footnote
This is a precursor to invasive germ cell tumors.
284
List some types of nonseminomatous germ cell tumors.
* Embryonal carcinoma
* Yolk sac tumor, postpubertal type
* Choriocarcinoma
* Teratoma, postpubertal type
* Teratoma with somatic-type malignancy
## Footnote
These tumors are classified as nonseminomatous germ cell tumors.
285
What is the lifetime risk of developing germ cell tumors highest?
Northern Europe and New Zealand
## Footnote
The lowest risk is observed in Africa and Asia.
286
What was the predicted number of new cases of germ cell tumors in the United States in 2019?
9560 new cases
## Footnote
There were also predicted 410 deaths from germ cell tumors in the same year.
287
What are some environmental factors contributing to germ cell tumor development?
* Cryptorchidism
* Environmental exposures
* Population migration studies
## Footnote
These factors suggest a link between environmental influences and the incidence of germ cell tumors.
288
What genetic factors are associated with germ cell tumor development?
* Germline variants in KIT, BAK
* KIT mutation
* Isochromosome 12p
## Footnote
These genetic factors contribute to the pathogenesis of germ cell tumors.
289
True or False: Testicular germ cell tumors predominantly affect males older than 45 years.
False
## Footnote
GCTs commonly affect Caucasian males between 15 and 45 years of age.
290
Fill in the blank: The most common benign tumor that occurs near the testis is the _______.
Adenomatoid tumor
## Footnote
This tumor can be identified intraoperatively, potentially sparing the patient from orchiectomy.
291
Where do infections in the male reproductive system invariably begin?
Epididymis
## Footnote
Infections can spread to the testis from the epididymis.
292
What is the most common benign paratesticular tumor?
Adenomatoid tumor
## Footnote
Adenomatoid tumors are mesothelial in nature and typically occur near the upper pole of the epididymis.
293
What are the common malignant paratesticular tumors in children and adults?
Children: Rhabdomyosarcomas, Adults: Liposarcomas
## Footnote
These tumors are the most frequently observed malignant paratesticular tumors.
294
What percentage of testicular neoplasms are germ cell tumors (GCTs)?
95%
## Footnote
GCTs are responsible for the overwhelming majority of testicular lesions.
295
What is the classification of noninvasive germ cell neoplasia?
Germ cell neoplasia in situ
## Footnote
This is a precursor to invasive germ cell tumors.
296
List some types of nonseminomatous germ cell tumors.
* Embryonal carcinoma
* Yolk sac tumor, postpubertal type
* Choriocarcinoma
* Teratoma, postpubertal type
* Teratoma with somatic-type malignancy
## Footnote
These tumors are classified as nonseminomatous germ cell tumors.
297
What is the lifetime risk of developing germ cell tumors highest?
Northern Europe and New Zealand
## Footnote
The lowest risk is observed in Africa and Asia.
298
What was the predicted number of new cases of germ cell tumors in the United States in 2019?
9560 new cases
## Footnote
There were also predicted 410 deaths from germ cell tumors in the same year.
299
What are some environmental factors contributing to germ cell tumor development?
* Cryptorchidism
* Environmental exposures
* Population migration studies
## Footnote
These factors suggest a link between environmental influences and the incidence of germ cell tumors.
300
What genetic factors are associated with germ cell tumor development?
* Germline variants in KIT, BAK
* KIT mutation
* Isochromosome 12p
## Footnote
These genetic factors contribute to the pathogenesis of germ cell tumors.
301
True or False: Testicular germ cell tumors predominantly affect males older than 45 years.
False
## Footnote
GCTs commonly affect Caucasian males between 15 and 45 years of age.
302
Fill in the blank: The most common benign tumor that occurs near the testis is the _______.
Adenomatoid tumor
## Footnote
This tumor can be identified intraoperatively, potentially sparing the patient from orchiectomy.
303
What is testicular dysgenesis syndrome associated with?
Cryptorchidism, hypospadias, and poor sperm quality
## Footnote
These conditions may be increased by in utero exposures to pesticides and nonsteroidal estrogens.
304
What is the risk factor for cryptorchidism in testicular germ cell tumors (GCTs)?
Approximately 10%
## Footnote
Cryptorchidism is a significant risk factor for developing testicular tumors.
305
How much does Klinefelter syndrome increase the risk of developing mediastinal GCTs?
50 times normal
## Footnote
Patients with Klinefelter syndrome do not develop testicular tumors.
306
What is the relative risk of GCTs in fathers and sons of affected patients?
Four times higher than normal
## Footnote
The risk is 8 to 10 times higher in brothers.
307
Which genes have been linked to familial GCT risk?
Variants in genes encoding the ligand for the receptor tyrosine kinase KIT and BAK
## Footnote
BAK is an important inducer of apoptotic cell death.
308
What is the cell of origin for germ cell tumors (GCTs)?
A primordial germ cell with an acquired defect in differentiation.
309
What is germ cell neoplasia in situ?
A precursor lesion found in about 90% of testes involved by germ cell neoplasms
## Footnote
It is associated with all types of GCTs except spermatocytic tumor and unusual types that arise in infancy.
310
What chromosomal alteration is strongly associated with the progression to invasive GCTs?
Reduplication of the short arm of chromosome 12 (isochromosome 12p).
311
What is the peak incidence age for seminomas?
In the fourth decade.
312
What is the most common type of germ cell tumor?
Seminoma
## Footnote
Seminomas make up about 50% of testicular germ cell tumors.
313
What is the typical morphology of seminomas?
Bulky masses, homogeneous gray-white lobulated cut surface, usually devoid of hemorrhage or necrosis.
314
What immunohistochemical markers are seminoma cells typically positive for?
KIT, OCT3/4, and podoplanin
## Footnote
They are negative for cytokeratin.
315
What percentage of seminomas contain syncytiotrophoblasts?
Approximately 15%.
316
What characterizes spermatocytic tumors?
They represent 1% to 2% of all testicular germ cell neoplasms and generally occur in individuals older than 65 years.
317
Do spermatocytic tumors metastasize?
No, they do not metastasize.
318
What is the prognosis for spermatocytic tumors when treated by surgical resection?
Excellent prognosis.
319
What is testicular dysgenesis syndrome associated with?
Cryptorchidism, hypospadias, and poor sperm quality
## Footnote
These conditions may be increased by in utero exposures to pesticides and nonsteroidal estrogens.
320
What is the risk factor for cryptorchidism in testicular germ cell tumors (GCTs)?
Approximately 10%
## Footnote
Cryptorchidism is a significant risk factor for developing testicular tumors.
321
How much does Klinefelter syndrome increase the risk of developing mediastinal GCTs?
50 times normal
## Footnote
Patients with Klinefelter syndrome do not develop testicular tumors.
322
What is the relative risk of GCTs in fathers and sons of affected patients?
Four times higher than normal
## Footnote
The risk is 8 to 10 times higher in brothers.
323
Which genes have been linked to familial GCT risk?
Variants in genes encoding the ligand for the receptor tyrosine kinase KIT and BAK
## Footnote
BAK is an important inducer of apoptotic cell death.
324
What is the cell of origin for germ cell tumors (GCTs)?
A primordial germ cell with an acquired defect in differentiation.
325
What is germ cell neoplasia in situ?
A precursor lesion found in about 90% of testes involved by germ cell neoplasms
## Footnote
It is associated with all types of GCTs except spermatocytic tumor and unusual types that arise in infancy.
326
What chromosomal alteration is strongly associated with the progression to invasive GCTs?
Reduplication of the short arm of chromosome 12 (isochromosome 12p).
327
What is the peak incidence age for seminomas?
In the fourth decade.
328
What is the most common type of germ cell tumor?
Seminoma
## Footnote
Seminomas make up about 50% of testicular germ cell tumors.
329
What is the typical morphology of seminomas?
Bulky masses, homogeneous gray-white lobulated cut surface, usually devoid of hemorrhage or necrosis.
330
What immunohistochemical markers are seminoma cells typically positive for?
KIT, OCT3/4, and podoplanin
## Footnote
They are negative for cytokeratin.
331
What percentage of seminomas contain syncytiotrophoblasts?
Approximately 15%.
332
What characterizes spermatocytic tumors?
They represent 1% to 2% of all testicular germ cell neoplasms and generally occur in individuals older than 65 years.
333
Do spermatocytic tumors metastasize?
No, they do not metastasize.
334
What is the prognosis for spermatocytic tumors when treated by surgical resection?
Excellent prognosis.
335
What is a seminoma?
A type of germ cell tumor characterized by sheets of pale tumor cells with poorly demarcated lobules and reactive lymphocytes
## Footnote
Associated with germ cell neoplasia in situ, lacks isochromosome 12p, and is typically associated with gain of chromosome 9q.
336
What histological features are seen in embryonal carcinoma?
Large cells with distinct cell borders, pale nuclei, prominent nucleoli, and abundant cytoplasm
## Footnote
It stains positively for OCT3/4, cytokeratin, and is negative for KIT and podoplanin.
337
What are the three populations of cells found in spermatocytic tumor?
1. Medium-sized cells with round nuclei and spireme-type chromatin
2. Smaller cells with dense chromatin
3. Scattered giant cells (uninucleate or multinucleate)
## Footnote
Spermatocytic tumor lacks inflammatory infiltrates and syncytiotrophoblasts.
338
Fill in the blank: Yolk sac tumor is also known as _______.
[endodermal sinus tumor]
339
In which age group are prepubertal yolk sac tumors most common?
Infants and children up to 3 years of age
## Footnote
They have a very good prognosis in this age group.
340
What is the peak incidence age group for embryonal carcinoma?
20- to 30-year-old age group
## Footnote
This is about a decade earlier than that of seminoma.
341
True or False: Embryonal carcinoma is less aggressive than seminoma.
False
342
What is a characteristic gross appearance of embryonal carcinoma?
Variegated appearance due to foci of hemorrhage or necrosis
## Footnote
It often extends through the tunica albuginea into the epididymis or spermatic cord.
343
What histological pattern do embryonal carcinomas tend to exhibit?
Alveolar or tubular patterns with possible papillary folds
## Footnote
More undifferentiated lesions may display sheets of cells with cleft-like spaces.
344
What is the common feature of neoplastic cells in embryonal carcinoma?
Large, anaplastic cells with hyperchromatic nuclei and prominent nucleoli
## Footnote
The cell borders are usually indistinct.
345
What does the term teratoma refer to?
GCTs having various cellular or organoid components reminiscent of normal derivatives of more than one germ layer.
346
At what ages can teratomas occur?
They may occur at any age from infancy to adulthood.
347
What is the prevalence of pure teratomas in infants and children?
Pure teratoma is fairly common in infants and children, referred to as the 'prepubertal type.'
348
What percentage of GCTs do pure teratomas constitute in adults?
Pure teratomas constitute 2% to 3% of GCTs in adults.
349
How do prepubertal teratomas differ biologically from adult teratomas?
Prepubertal teratomas are not associated with germ cell neoplasia in situ or isochromosome 12p and pursue a benign course.
350
What is a significant histological feature of pre- and postpubertal yolk sac tumors?
Prepubertal tumors are not associated with germ cell neoplasia in situ and lack other germ cell elements.
351
Describe the histological appearance of yolk sac tumors.
Typically composed of a lace-like (reticular) network of medium-sized cuboidal, flattened, or spindled cells.
352
What structures may be seen in approximately 50% of yolk sac tumors?
Structures resembling endodermal sinuses (Schiller-Duval bodies).
353
What is characteristic of yolk sac tumor cells?
Eosinophilic, hyaline-like globules containing a-fetoprotein (AFP) and a,-antitrypsin.
354
What is choriocarcinoma?
A highly malignant type of GCT, constituting less than 1% of all GCTs.
355
What is typically elevated in choriocarcinoma?
Serum hCG is invariably elevated.
356
What are the primary cell types in choriocarcinoma?
Syncytiotrophoblasts and cytotrophoblasts.
357
What is the usual size of primary choriocarcinoma tumors?
Typically small, rarely larger than 5 cm in diameter.
358
What types of tissues are usually found in teratomas presenting in adult males?
Variety of tissues including solid, cartilaginous, and cystic areas.
359
What types of cells or structures may be seen microscopically in teratomas?
Differentiated cells or organoid structures such as neural tissue, muscle bundles, and cartilage.
360
What phenomenon may occur in postpubertal teratomas?
Teratoma with somatic-type malignant transformation.
361
Fill in the blank: Choriocarcinoma is associated with widespread _______.
metastasis.
362
True or False: Adult teratomas are commonly benign.
False.
363
What does the term teratoma refer to?
GCTs having various cellular or organoid components reminiscent of normal derivatives of more than one germ layer.
364
At what ages can teratomas occur?
They may occur at any age from infancy to adulthood.
365
What is the prevalence of pure teratomas in infants and children?
Pure teratoma is fairly common in infants and children, referred to as the 'prepubertal type.'
366
What percentage of GCTs do pure teratomas constitute in adults?
Pure teratomas constitute 2% to 3% of GCTs in adults.
367
How do prepubertal teratomas differ biologically from adult teratomas?
Prepubertal teratomas are not associated with germ cell neoplasia in situ or isochromosome 12p and pursue a benign course.
368
What is a significant histological feature of pre- and postpubertal yolk sac tumors?
Prepubertal tumors are not associated with germ cell neoplasia in situ and lack other germ cell elements.
369
Describe the histological appearance of yolk sac tumors.
Typically composed of a lace-like (reticular) network of medium-sized cuboidal, flattened, or spindled cells.
370
What structures may be seen in approximately 50% of yolk sac tumors?
Structures resembling endodermal sinuses (Schiller-Duval bodies).
371
What is characteristic of yolk sac tumor cells?
Eosinophilic, hyaline-like globules containing a-fetoprotein (AFP) and a,-antitrypsin.
372
What is choriocarcinoma?
A highly malignant type of GCT, constituting less than 1% of all GCTs.
373
What is typically elevated in choriocarcinoma?
Serum hCG is invariably elevated.
374
What are the primary cell types in choriocarcinoma?
Syncytiotrophoblasts and cytotrophoblasts.
375
What is the usual size of primary choriocarcinoma tumors?
Typically small, rarely larger than 5 cm in diameter.
376
What types of tissues are usually found in teratomas presenting in adult males?
Variety of tissues including solid, cartilaginous, and cystic areas.
377
What types of cells or structures may be seen microscopically in teratomas?
Differentiated cells or organoid structures such as neural tissue, muscle bundles, and cartilage.
378
What phenomenon may occur in postpubertal teratomas?
Teratoma with somatic-type malignant transformation.
379
Fill in the blank: Choriocarcinoma is associated with widespread _______.
metastasis.
380
True or False: Adult teratomas are commonly benign.
False.
381
What is a teratoma of the testis characterized by?
A variegated cut surface with cysts reflecting the presence of multiple tissue types.
## Footnote
Teratomas can contain various types of tissues, including hair, teeth, and skin.
382
Why is it important to recognize a somatic-type malignancy arising in a teratoma?
These secondary tumors are chemoresistant; thus, the only hope for cure resides in resection of the tumor.
383
What is retained by non-germ cell malignancies in teratomas that proves a clonal relationship to the preceding teratoma?
Isochromosome 12p.
384
How do prepubertal teratomas differ from postpubertal teratomas?
Prepubertal teratomas produce distinct elements arranged into structures that more closely resemble normal tissue.
385
What are dermoid cysts typically composed of?
Hair, teeth, and skin.
386
What percentage of germ cell tumors (GCTs) are composed of more than one type?
About 60%.
387
Name common mixtures found in mixed germ cell tumors.
* Teratoma with embryonal carcinoma
* Yolk sac tumor with seminoma
* Embryonal carcinoma with teratoma.
388
What is a characteristic feature of testicular germ cell tumors?
Painless enlargement of the testis.
389
What is the standard management for a solid testicular mass?
Radical orchiectomy based on the presumption of malignancy.
390
What is the risk associated with biopsy of a testicular neoplasm?
Risk of tumor spillage, necessitating excision of the scrotal skin in addition to orchiectomy.
391
What is the primary mode of spread for testicular tumors?
Lymphatic spread.
392
Which nodes are typically the first involved in the spread of testicular tumors?
Retroperitoneal para-aortic nodes.
393
What are common sites for hematogenous spread of testicular tumors?
* Lungs
* Liver
* Brain
* Bones.
394
How does the histology of metastases and distant recurrences differ from that of the testicular lesion?
It may differ because GCTs are derived from pluripotent germ cells.
395
What are some serum biomarkers secreted by germ cell tumors?
* hCG
* AFP
* Lactate dehydrogenase.
396
What does marked elevation of serum AFP or hCG levels indicate?
Yolk sac tumor and syncytiotrophoblastic elements, respectively.
397
In what ways are serum markers valuable in the context of testicular tumors?
* Initial evaluation of testicular masses
* Staging of testicular GCTs
* Assessing tumor burden
* Monitoring response to therapy.
398
What factors largely determine the therapy and prognosis of testicular tumors?
Clinical and pathologic stage and histologic type.
399
What is the prognosis for seminoma?
Best prognosis; more than 95% of patients with stage I and II seminoma are cured by orchiectomy with or without chemotherapy or radiotherapy.
400
What is the remission rate for nonseminomatous GCT patients with aggressive chemotherapy?
Approximately 90% achieve complete remission.
401
True or False: Pure embryonal carcinoma behaves less aggressively than mixed GCTs.
False.
402
What type of germ cell tumor has a poor prognosis?
Pure choriocarcinoma and mixed GCT with predominantly choriocarcinoma.
403
What are sex cord-gonadal stromal tumors subclassified based on?
Histogenesis and differentiation
404
What are the two most important members of the sex cord-gonadal stromal tumors?
Leydig cell tumors and Sertoli cell tumors
405
What pathologic features are correlated with malignancy in sex cord-stromal tumors of the testis?
Large size (greater than 5 cm), necrosis, infiltrative borders, anaplasia, mitotic activity, vascular-lymphatic invasion, extratesticular extension
406
What hormones do Leydig cell tumors often elaborate?
Androgens, estrogens, corticosteroids
407
What is the most common presenting feature of Leydig cell tumors?
Testicular swelling
408
What hormonal effect may be dominant in children with Leydig cell tumors?
Sexual precocity
409
Which syndromes are associated with Leydig cell tumors?
* Klinefelter syndrome
* Cryptorchidism
* Hereditary leiomyomatosis and renal cell carcinoma syndrome
410
What percentage of Leydig cell tumors in adults are malignant?
Approximately 10%
411
What is the typical morphology of Leydig cell tumors?
Circumscribed nodules, usually less than 5 cm, golden brown, homogeneous appearance
412
What histological features are characteristic of Leydig cell tumors?
Large size, round or polygonal outlines, abundant granular eosinophilic cytoplasm, round central nucleus, rod-shaped crystalloids of Reinke
413
What are Sertoli cell tumors typically associated with?
* Carney complex
* Peutz-Jeghers syndrome
* Familial adenomatosis polyposis syndrome
414
How do Sertoli cell tumors typically present?
As a testicular mass
415
What is the appearance of Sertoli cell tumors on cut surface?
Firm, small nodules with homogeneous gray-white to yellow cut surface
416
What histological arrangement do Sertoli cell tumors exhibit?
Trabeculae that form cord-like structures and tubules
417
What is the percentage of Sertoli cell tumors that are malignant?
Approximately 10%
418
What are gonadoblastomas comprised of?
A mixture of germ cells and gonadal stromal elements
419
In what context do gonadoblastomas typically arise?
In gonads with some form of testicular dysgenesis
420
What is the most common type of testicular neoplasm in men older than 60 years of age?
Primary testicular lymphomas
421
What percentage of testicular neoplasms do primary testicular lymphomas account for?
5%
422
What is the common histological type of testicular lymphoma?
* Diffuse large B-cell lymphoma
* Burkitt lymphoma
* Epstein-Barr virus-positive extranodal NK/T-cell lymphoma
423
What are the key concepts regarding testicular tumors?
* GCTs are the most common tumor types, accounting for 95% of testicular neoplasms
* Risk factors include cryptorchidism, infertility, prior history of GCT
* Germ cell neoplasia in situ is a precursor lesion associated with most GCTs
* Common types of GCTs: seminoma, embryonal carcinoma, yolk sac tumors, choriocarcinoma, teratoma
* Testicular GCTs are divided into seminomas and nonseminomatous tumors
* hCG, AFP, and lactate dehydrogenase are valuable blood biomarkers
* Non-GCTs include sex cord-gonadal stromal tumors and non-Hodgkin lymphoma
424
What is a hydrocele?
Accumulation of serous fluid in the tunica vaginalis
425
What does transillumination help to define in the case of hydrocele?
Clear, translucent character of the contained fluid
426
What is a hematocele?
Collection of blood in the tunica vaginalis
427
What is a chylocele?
Accumulation of lymph in the tunica vaginalis
428
What is a spermatocele?
Small cystic accumulation of semen in dilated efferent ducts or ducts of the rete testis
429
What is a varicocele?
Dilated vein in the spermatic cord
430
True or False: Varicoceles may be asymptomatic.
True
431
What condition can varicoceles contribute to in some men?
Infertility
432
What is the prostate?
A retroperitoneal organ encircling the neck of the bladder and urethra, lacking a distinct capsule.
433
What is the approximate weight of a normal adult prostate?
Approximately 20 g.
434
Name the four distinct regions of the prostate.
* Peripheral zone
* Central zone
* Transition zone
* Periurethral zone
435
Where do most hyperplasias arise in the prostate?
In the transition zone.
436
Where do most carcinomas originate in the prostate?
In the peripheral zone.
437
What are the two layers of cells that line the prostate glands?
* Basal layer of low cuboidal basal epithelium
* Columnar secretory cells
438
What controls the growth and survival of prostatic cells?
Testicular androgens.
439
What happens to the prostate after castration?
Widespread apoptosis of prostatic epithelium and atrophy of the prostate.
440
What are the three pathologic processes that frequently affect the prostate gland?
* Inflammation
* Benign prostatic hypertrophy (BPH)
* Tumors
441
What is the most common pathologic process affecting the prostate gland?
Benign prostatic hypertrophy (BPH).
442
True or False: Prostatic carcinoma is an uncommon condition in older men.
False.
443
What is prostatitis?
Inflammation of the prostate gland.
444
What typically causes acute bacterial prostatitis?
Bacteria similar to those that cause urinary tract infections, often E. coli.
445
How do bacteria usually reach the prostate in acute bacterial prostatitis?
Through the reflux of contaminated urine from the posterior urethra or urinary bladder.
446
What are the clinical features of acute bacterial prostatitis?
* Fever
* Chills
* Dysuria
447
What is a contraindication for biopsy in acute prostatitis?
It may lead to sepsis.
448
What symptoms are associated with chronic bacterial prostatitis?
* Low back pain
* Dysuria
* Perineal discomfort
* Suprapubic discomfort
449
What is the most common form of prostatitis?
Chronic abacterial prostatitis.
450
Fill in the blank: Chronic abacterial prostatitis is often referred to as _______.
[chronic pelvic pain syndrome]
451
What is granulomatous prostatitis?
Prostatitis that may be caused by a specific infectious agent or a pattern of tissue reaction to noninfectious stimuli.
452
What is often the most common cause of granulomatous prostatitis in the United States?
Instillation of BCG for treatment.
453
What is the most common benign prostatic disease in men older than age 50?
Benign Prostatic Hyperplasia (BPH)
## Footnote
BPH is also referred to as nodular hyperplasia.
454
What percentage of white American men over 50 have moderate to severe symptoms of BPH?
Approximately 30%
## Footnote
Histologic evidence of BPH is found in up to 90% of men by age 80.
455
What hormone is primarily responsible for the development of BPH?
Dihydrotestosterone (DHT)
## Footnote
DHT is formed from testosterone through the action of type 2 5a-reductase.
456
What is the role of type 2 5a-reductase in the prostate?
It converts testosterone into dihydrotestosterone (DHT)
## Footnote
Type 2 5a-reductase is expressed primarily in stromal cells.
457
What is the effect of DHT binding to androgen receptors (ARs) in prostate cells?
It stimulates the transcription of androgen-dependent genes
## Footnote
This includes growth factors and their receptors.
458
List two important growth factors upregulated by DHT in prostatic growth.
* Fibroblast growth factor (FGF) family
* Transforming growth factor (TGF) B
## Footnote
FGFs are produced by stromal cells and TGFß serves as a mitogen for fibroblasts.
459
True or False: BPH is considered a premalignant lesion.
False
## Footnote
BPH is not a premalignant lesion.
460
What role do estrogens play in the pathogenesis of BPH?
They contribute by tipping the balance toward proliferation
## Footnote
Estrogens have opposing effects on prostate cells via ERa and ERß.
461
What happens to the weight of the prostate in BPH?
It often increases three- to fivefold (60 to 100 g)
## Footnote
Greater enlargement can occur in some cases.
462
Fill in the blank: DHT is more potent than testosterone because it has a higher affinity for _______.
androgen receptors (ARs)
## Footnote
DHT forms a more stable complex with ARs.
463
What are the two different forms of estrogen receptors mentioned in the context of BPH?
* ERa
* ERß
## Footnote
These receptors have opposing proliferative and antiproliferative effects on prostate cells.
464
What is nonspecific granulomatous prostatitis a reaction to?
Secretions from ruptured prostatic ducts
## Footnote
It is relatively common.
465
What is the significance of finding granulomas in the prostate in the context of bladder cancer?
It is of no clinical significance and requires no treatment
## Footnote
Fungal granulomatous prostatitis is typically seen in immunocompromised hosts.
466
What are the mechanisms through which estrogens affect the prostate?
* Apoptosis
* Aromatase expression
* Paracrine regulation via prostaglandin E2
## Footnote
These mechanisms contribute to BPH pathogenesis.
467
What is the most common benign prostatic disease in men older than age 50?
Benign Prostatic Hyperplasia (BPH)
## Footnote
BPH is also referred to as nodular hyperplasia.
468
What percentage of white American men over 50 have moderate to severe symptoms of BPH?
Approximately 30%
## Footnote
Histologic evidence of BPH is found in up to 90% of men by age 80.
469
What hormone is primarily responsible for the development of BPH?
Dihydrotestosterone (DHT)
## Footnote
DHT is formed from testosterone through the action of type 2 5a-reductase.
470
What is the role of type 2 5a-reductase in the prostate?
It converts testosterone into dihydrotestosterone (DHT)
## Footnote
Type 2 5a-reductase is expressed primarily in stromal cells.
471
What is the effect of DHT binding to androgen receptors (ARs) in prostate cells?
It stimulates the transcription of androgen-dependent genes
## Footnote
This includes growth factors and their receptors.
472
List two important growth factors upregulated by DHT in prostatic growth.
* Fibroblast growth factor (FGF) family
* Transforming growth factor (TGF) B
## Footnote
FGFs are produced by stromal cells and TGFß serves as a mitogen for fibroblasts.
473
True or False: BPH is considered a premalignant lesion.
False
## Footnote
BPH is not a premalignant lesion.
474
What role do estrogens play in the pathogenesis of BPH?
They contribute by tipping the balance toward proliferation
## Footnote
Estrogens have opposing effects on prostate cells via ERa and ERß.
475
What happens to the weight of the prostate in BPH?
It often increases three- to fivefold (60 to 100 g)
## Footnote
Greater enlargement can occur in some cases.
476
Fill in the blank: DHT is more potent than testosterone because it has a higher affinity for _______.
androgen receptors (ARs)
## Footnote
DHT forms a more stable complex with ARs.
477
What are the two different forms of estrogen receptors mentioned in the context of BPH?
* ERa
* ERß
## Footnote
These receptors have opposing proliferative and antiproliferative effects on prostate cells.
478
What is nonspecific granulomatous prostatitis a reaction to?
Secretions from ruptured prostatic ducts
## Footnote
It is relatively common.
479
What is the significance of finding granulomas in the prostate in the context of bladder cancer?
It is of no clinical significance and requires no treatment
## Footnote
Fungal granulomatous prostatitis is typically seen in immunocompromised hosts.
480
What are the mechanisms through which estrogens affect the prostate?
* Apoptosis
* Aromatase expression
* Paracrine regulation via prostaglandin E2
## Footnote
These mechanisms contribute to BPH pathogenesis.
481
What is Benign Prostatic Hyperplasia (BPH)?
BPH is characterized by proliferation of benign stromal and glandular elements.
482
What is the major hormonal stimulus for proliferation in BPH?
DHT, an androgen derived from testosterone.
483
Which zones of the prostate are most commonly affected by BPH?
The inner periurethral zone and transition zone.
484
What are the main clinical symptoms of BPH?
Increased urinary frequency, nocturia, difficulty starting/stopping urine stream, overflow dribbling, dysuria.
485
What complications can arise from urinary obstruction due to BPH?
Bladder hypertrophy, distention, urine retention, recurrent urinary tract infections.
486
What is the gold standard for managing symptomatic BPH?
Transurethral resection of the prostate (TURP).
487
What types of medications are used to manage BPH?
α-adrenergic blockers and 5α-reductase inhibitors.
488
Fill in the blank: BPH may lead to _______ retention requiring emergency catheterization.
acute urinary
489
What are alternative procedures developed for BPH treatment?
* High-intensity focused ultrasound (HIFU)
* Laser therapy
* Hyperthermia
* Transurethral electrovaporization
* Radiofrequency ablation
490
What is the most common form of cancer in men in the United States?
Adenocarcinoma of the prostate.
491
How many new cases of prostate cancer were expected in 2019?
174,650 new cases.
492
What percentage of all male cancers does prostate cancer account for?
20%.
493
What is the second leading cause of cancer-related death in men?
Prostate cancer.
494
What factors are associated with prostate cancer?
* Dietary exposure
* Chronic inflammation
* Androgens
495
What is the leading cause of cancer death in men?
Prostate cancer
## Footnote
Surpassed only by lung cancer.
496
What is the incidence of prostate cancer in men aged 50s compared to those aged 70-80?
20% in 50s; approximately 70% in 70-80 years
## Footnote
Based on autopsy studies.
497
What factors contribute to the incidence of prostate cancer across geographic locales?
Environmental exposures and inherited genetic factors
498
How does the incidence of prostate cancer differ between Japanese individuals in the U.S. and those in Japan?
Higher in the U.S.; about 50% of the incidence in African Americans
499
What roles do androgens and androgen receptor (AR) function play in prostate cancer?
Central roles in development, progression, and treatment
500
What is hypothesized to damage prostatic epithelium and lead to cancer development?
Exposure to carcinogens, estrogens, and oxidants
501
What dietary component is linked to an increased risk of prostate cancer?
Consumption of charred red meats and animal fats
502
What type of stress may lead to cell injury and inflammation in prostate epithelium?
Oxidant stress
503
Which enzyme's polymorphisms are linked to prostate cancer risk?
Glutathione-S-transferase (GSTP1)
504
What is the increased risk for men with first-degree relatives affected by prostate cancer?
Twofold increased risk
505
Which important oncogene's expression is influenced by common genetic variants associated with prostate cancer risk?
MYC
506
What mutations are linked to high risk of early-onset aggressive prostate cancer?
Loss-of-function mutations in BRCA2 and DNA mismatch repair genes
507
What gene is associated with a severalfold increased risk of prostate cancer?
HOXB13
508
What is the role of androgens in prostate cancer cell growth?
Androgens induce the expression of pro-growth and pro-survival genes
509
What therapeutic effects do castration or antiandrogens have on prostate cancer?
Usually induce disease regression
510
What happens to most tumors over time with respect to androgen blockade?
Become resistant to androgen blockade
511
What is one mechanism by which tumors escape androgen blockade?
Acquisition of hypersensitivity to low levels of androgen
512
What is ligand-independent AR activation in prostate cancer?
Activation via splice variants that lack the ligand binding domain or mutations allowing activation by non-androgen ligands.
513
What are common genetic alterations in prostate cancer?
Chromosomal rearrangements, particularly involving ETS family transcription factor genes like ERG or ETV1.
514
What gene is commonly silenced in prostate cancer?
The gene encoding p27, an inhibitor of cyclin-dependent kinases.
515
Which two genes are frequently altered in prostate carcinoma?
* MYC (amplification)
* PTEN (deletion)
516
What is a typical feature of late-stage prostate cancer?
Loss of TP53 and deletions of RB.
517
What role does DNA methylation play in prostate cancer?
It modifies gene expression, leading to distinct subsets of prostate cancers.
518
What is the significance of GSTP1 gene silencing in prostate cancer?
It downregulates GSIP1 expression, potentially enhancing genotoxic effects of carcinogens.
519
What is prostatic intraepithelial neoplasia (PIN)?
A putative precursor lesion for prostate cancer.
520
Where does carcinoma of the prostate typically arise?
In the peripheral zone of the gland, classically in a posterior location.
521
What is the histological appearance of most adenocarcinomas in prostate cancer?
Glands arranged in well-defined patterns, smaller than benign glands, lined by cuboidal or low columnar epithelium.
522
What are the common sites of metastasis for prostate cancer?
* Lymphatics to obturator nodes and para-aortic nodes
* Hematogenous spread to bones
523
What type of bone metastases are typical in prostate cancer?
Osteoblastic metastases.
524
What are the bones most commonly involved in prostate cancer metastasis?
* Lumbar spine
* Proximal femur
* Pelvis
* Thoracic spine
* Ribs
525
What diagnostic challenge is often faced in identifying prostate cancer?
Scant tissue in needle biopsies and benign glands admixed with malignant glands.
526
What is a specific histological finding that can indicate prostate cancer?
Perineural invasion.
527
True or False: Prostate cancer typically shows marked pleomorphism.
False.
528
Fill in the blank: The common variant of prostate cancer is known as _______.
[acinar adenocarcinoma].
529
What is ligand-independent AR activation in prostate cancer?
Activation via splice variants that lack the ligand binding domain or mutations allowing activation by non-androgen ligands.
530
What are common genetic alterations in prostate cancer?
Chromosomal rearrangements, particularly involving ETS family transcription factor genes like ERG or ETV1.
531
What gene is commonly silenced in prostate cancer?
The gene encoding p27, an inhibitor of cyclin-dependent kinases.
532
Which two genes are frequently altered in prostate carcinoma?
* MYC (amplification)
* PTEN (deletion)
533
What is a typical feature of late-stage prostate cancer?
Loss of TP53 and deletions of RB.
534
What role does DNA methylation play in prostate cancer?
It modifies gene expression, leading to distinct subsets of prostate cancers.
535
What is the significance of GSTP1 gene silencing in prostate cancer?
It downregulates GSIP1 expression, potentially enhancing genotoxic effects of carcinogens.
536
What is prostatic intraepithelial neoplasia (PIN)?
A putative precursor lesion for prostate cancer.
537
Where does carcinoma of the prostate typically arise?
In the peripheral zone of the gland, classically in a posterior location.
538
What is the histological appearance of most adenocarcinomas in prostate cancer?
Glands arranged in well-defined patterns, smaller than benign glands, lined by cuboidal or low columnar epithelium.
539
What are the common sites of metastasis for prostate cancer?
* Lymphatics to obturator nodes and para-aortic nodes
* Hematogenous spread to bones
540
What type of bone metastases are typical in prostate cancer?
Osteoblastic metastases.
541
What are the bones most commonly involved in prostate cancer metastasis?
* Lumbar spine
* Proximal femur
* Pelvis
* Thoracic spine
* Ribs
542
What diagnostic challenge is often faced in identifying prostate cancer?
Scant tissue in needle biopsies and benign glands admixed with malignant glands.
543
What is a specific histological finding that can indicate prostate cancer?
Perineural invasion.
544
True or False: Prostate cancer typically shows marked pleomorphism.
False.
545
Fill in the blank: The common variant of prostate cancer is known as _______.
[acinar adenocarcinoma].
546
What distinguishes benign glands from cancerous glands in prostatic tissue?
Benign glands contain basal cells, which are absent in cancerous glands.
## Footnote
This difference can be highlighted using immunohistologic markers that stain basal cells.
547
What is a useful immunohistologic marker for prostate cancer?
a-methylacyl coenzyme A racemase (AMACR) is a useful marker that is upregulated in prostate cancer.
## Footnote
Most prostate cancers are positive for AMACR, with sensitivity varying from 82% to 100% across studies.
548
What is prostatic intraepithelial neoplasia (PIN)?
PIN consists of architecturally benign large, branching prostatic acini lined by atypical cells with prominent nucleoli.
## Footnote
Unlike malignant glands, glands involved by PIN retain a layer of basal cells and an intact basement membrane.
549
What are the most important prognostic factors in prostate cancer?
Grade and stage are the most important prognostic factors in prostate cancer.
550
What grading system is used for prostate cancer?
The Gleason system is used to grade prostate cancer based on glandular patterns of growth.
551
What does Grade 1 in the Gleason system indicate?
Grade 1 corresponds to well-differentiated tumors with uniform and round neoplastic glands packed into well-circumscribed nodules.
552
What characterizes Grade 5 tumors in the Gleason system?
Grade 5 tumors do not form glands; tumor cells infiltrate the stroma in cords, sheets, and solid nests.
553
True or False: Most prostate cancers are negative for AMACR.
False
## Footnote
Most prostate cancers are positive for AMACR.
554
Fill in the blank: The sensitivity of AMACR in detecting prostate cancer varies among studies from ______ to 100%.
[82%]
555
What is the relationship between PIN and prostatic carcinoma?
Approximately 80% of cases with prostatic carcinoma also harbor prostatic intraepithelial neoplasia (PIN).
556
What do atypical cells in PIN resemble?
Atypical cells in PIN may be cytologically identical to carcinoma.
557
What is the Gleason score used for?
It is used to grade prostate cancer based on the patterns of tumor cells.
558
How is the Gleason score calculated?
A primary grade is assigned to the dominant pattern and a secondary grade to the second most frequent pattern, which are then added together.
559
What Gleason scores are typically associated with potentially treatable cancers detected on needle biopsy?
Scores of 6 or 7.
560
What Gleason scores indicate advanced cancers that are less likely to be cured?
Scores of 8 through 10.
561
True or False: The Gleason score of prostate cancer typically changes significantly over several years.
False.
562
What are the five Grade Groups of Gleason scores?
* Grade Group I (<6)
* Grade Group II (3 + 4)
* Grade Group III (4 + 3)
* Grade Group IV (4 + 4/3 + 5/5 + 3)
* Grade Group V (4 + 5/5 + 4/5 + 5)
563
What does pTNM staging assess in prostatic cancer?
Tumor extent (T) and presence of nodal or distant metastasis (N and M).
564
What is the typical method for diagnosing localized prostate cancer?
Transrectal needle biopsy.
565
What role does serum prostate-specific antigen (PSA) play in prostate cancer?
It assists with diagnosis and management.
566
What is PSA and its function?
PSA is an androgen-regulated serine protease that cleaves and liquefies the seminal coagulum.
567
What are the limitations of PSA as a screening test for prostate cancer?
It has suboptimal sensitivity and specificity.
568
What are the clinical features of localized prostate cancer?
It is usually asymptomatic and discovered during a rectal examination or elevated serum PSA level.
569
What symptoms may patients with clinically advanced prostatic cancer present?
Symptoms of urinary obstruction.
570
What is the significance of digital rectal examination in prostate cancer detection?
It may detect early prostatic carcinomas but has low sensitivity and specificity.
571
Fill in the blank: A primary Gleason grade is assigned to the ________ pattern of the tumor.
dominant
572
Fill in the blank: The majority of potentially treatable prostate cancers detected on biopsy have Gleason scores of ________.
6 or 7
573
True or False: Elevated blood levels of PSA can occur with both localized and advanced cancer.
True.
574
What is the relationship between Gleason score and tumor aggressiveness over time?
Most commonly, the Gleason score remains stable over several years.
575
What is the most common malignancy in men in the United States?
Carcinoma of the prostate
## Footnote
It is especially common in older men.
576
Where do prostate carcinomas most commonly arise?
In the outer, peripheral gland
## Footnote
These may be palpable by rectal examination.
577
What are the two types of prostate cancer treatments typically used for high-risk localized prostate cancer?
* Surgery
* Radiation
## Footnote
Hormonal manipulation may also be included.
578
What is the Gleason grading system used for?
To grade prostate cancer
## Footnote
It strongly correlates with pathologic stage and prognosis.
579
What are the common driver mutations in prostate cancer?
* Gene rearrangements
* Overexpression of Ets family transcription factors (commonly ERG or ETV1)
## Footnote
These mutations lead to androgen dependency.
580
What is the significance of serum PSA measurement?
It is a useful but imperfect cancer-screening test
## Footnote
It has significant rates of false-negative and false-positive results.
581
What does pT3b indicate in the pTNM staging system?
Tumor invades seminal vesicles
## Footnote
This is part of the staging for prostatic adenocarcinoma.
582
What is the prognosis for patients who receive therapy for localized prostate cancer?
More than 90% can expect to live for 15 years
## Footnote
This applies to those treated with surgery or radiation.
583
What does PSA stand for?
Prostate-Specific Antigen
## Footnote
It is organ specific but not cancer specific.
584
What is the definition of pT2 in the pTNM system?
Organ confined
## Footnote
This indicates the extent of the primary tumor.
585
What type of adenocarcinoma may arise from prostatic ducts?
Ductal adenocarcinoma
## Footnote
It may present similarly to ordinary prostate cancer or show signs like hematuria.
586
What is colloid carcinoma of the prostate characterized by?
Abundant mucinous secretions in greater than 25% of the tumor
## Footnote
This type of carcinoma has a distinctive histological feature.
587
What treatment is often used for metastatic carcinoma of the prostate?
Androgen deprivation therapy
## Footnote
This is usually achieved by orchiectomy or administration of LHRH analogs.
588
True or False: Most localized prostate cancers are clinically significant.
False
## Footnote
Many are indolent and may lead to overtreatment.
589
Fill in the blank: Chronic administration of LHRH agonists desensitizes pituitary cells expressing LHRH receptors, suppressing the release of _______.
Luteinizing hormone (LH)
## Footnote
LH is required for testosterone production.
590
What is the significance of monitoring PSA concentrations after treatment?
It has great value in monitoring progressive or recurrent disease
## Footnote
This is crucial for patient management following prostate cancer treatment.
591
What is the most common malignancy in men in the United States?
Carcinoma of the prostate
## Footnote
It is especially common in older men.
592
Where do prostate carcinomas most commonly arise?
In the outer, peripheral gland
## Footnote
These may be palpable by rectal examination.
593
What are the two types of prostate cancer treatments typically used for high-risk localized prostate cancer?
* Surgery
* Radiation
## Footnote
Hormonal manipulation may also be included.
594
What is the Gleason grading system used for?
To grade prostate cancer
## Footnote
It strongly correlates with pathologic stage and prognosis.
595
What are the common driver mutations in prostate cancer?
* Gene rearrangements
* Overexpression of Ets family transcription factors (commonly ERG or ETV1)
## Footnote
These mutations lead to androgen dependency.
596
What is the significance of serum PSA measurement?
It is a useful but imperfect cancer-screening test
## Footnote
It has significant rates of false-negative and false-positive results.
597
What does pT3b indicate in the pTNM staging system?
Tumor invades seminal vesicles
## Footnote
This is part of the staging for prostatic adenocarcinoma.
598
What is the prognosis for patients who receive therapy for localized prostate cancer?
More than 90% can expect to live for 15 years
## Footnote
This applies to those treated with surgery or radiation.
599
What does PSA stand for?
Prostate-Specific Antigen
## Footnote
It is organ specific but not cancer specific.
600
What is the definition of pT2 in the pTNM system?
Organ confined
## Footnote
This indicates the extent of the primary tumor.
601
What type of adenocarcinoma may arise from prostatic ducts?
Ductal adenocarcinoma
## Footnote
It may present similarly to ordinary prostate cancer or show signs like hematuria.
602
What is colloid carcinoma of the prostate characterized by?
Abundant mucinous secretions in greater than 25% of the tumor
## Footnote
This type of carcinoma has a distinctive histological feature.
603
What treatment is often used for metastatic carcinoma of the prostate?
Androgen deprivation therapy
## Footnote
This is usually achieved by orchiectomy or administration of LHRH analogs.
604
True or False: Most localized prostate cancers are clinically significant.
False
## Footnote
Many are indolent and may lead to overtreatment.
605
Fill in the blank: Chronic administration of LHRH agonists desensitizes pituitary cells expressing LHRH receptors, suppressing the release of _______.
Luteinizing hormone (LH)
## Footnote
LH is required for testosterone production.
606
What is the significance of monitoring PSA concentrations after treatment?
It has great value in monitoring progressive or recurrent disease
## Footnote
This is crucial for patient management following prostate cancer treatment.
607
What is the most common treatment for prostate cancer?
Radical prostatectomy
## Footnote
This treatment is typically indicated for localized prostate cancer.
608
What is the prognosis for patients receiving hormonal manipulation therapy?
More than W% can expect to live for 15 years
## Footnote
The specific percentage (W%) is not provided in the text.
609
What type of carcinoma is characterized by abundant mucinous secretions in greater than 25% of the tumor?
Colloid carcinoma of the prostate
## Footnote
This type of carcinoma is noted for its distinct histological features.
610
What is the most aggressive variant of prostate cancer?
Small-cell carcinoma (neuroendocrine carcinoma)
## Footnote
This variant is associated with rapid progression and is often fatal.
611
What is a common consequence of antiandrogen therapies in typical prostate cancer?
Emergence of an androgen-independent sub-clone with a neuroendocrine phenotype
## Footnote
This phenomenon complicates treatment and may lead to recurrence.
612
What is the most common tumor to secondarily involve the prostate?
Urothelial cancer
## Footnote
This cancer can invade the prostate from the bladder or extend via CIS.
613
What are the two distinct patterns of urothelial cancer involvement in the prostate?
1. Large invasive urothelial cancers directly invade from the bladder
2. CIS of the bladder extends into the prostatic urethra and ducts
## Footnote
These patterns illustrate the pathways of cancer spread.
614
Fill in the blank: The same mesenchymal tumors that involve the bladder may also manifest in the _______.
Prostate
## Footnote
Mesenchymal tumors can affect multiple organs.
615
What unique tumors exist in the prostate derived from the prostatic stroma?
Unique mesenchymal tumors
## Footnote
These tumors are distinct from those affecting the bladder.
