Robbins Flashcards
Normal number of layers of urothelium
5-6
surface layer of urothelium
umbrella cells
T/F The lamina propria in the bladder has smooth muscle
T
T/F Bladder muscularis mucosa is composed of a single continuous layer of smooth muscle
False, it is composed of discontinuous wisps of smooth muscle from the lamina propria
In females, relaxation of pelvic support leads to prolapse (descent) of the uterus, pulling with it the floor of the bladder. Thus the bladder is protruded into the vagina, creating a pouch called
cystocele
most common cause of hydronephrosis in infants and children
Ureteropelvic junction (UPJ) obstruction
benign ureter tumor-like lesion often occurring in children, is composed of loose, vascularized connective tissue overlaid by urothelium
Fibroepithelial polyp
Unilateral ureteral obstruction typically results from
proximal intrinsic or extrinsic causes (e.g., stones, neoplasms etc.
bilateral ureteral obstruction arises from distal causes, such as
nodular hyperplasia of the prostate
most common and serious congenital anomaly where incompetence of the vesicoureteral valve allows bacteria to ascend the ureter into the renal pelvis
Vesicoureteral reflux
why are carcinoma that arise in bladder diverticula are on average more advanced in stage?
thin or absent musclularis propria
is a developmental failure in the anterior wall of the abdomen and the bladder and is associated with an increased risk of adenocarcinoma in the bladder remnant
Exstrophy of the bladder
T/F Urachal cysts are at increased risk for neoplastic transformation, mostly presenting as squamous carcinomas
False mostly present as adenocarcinomas
Predisposing factors for cystitis (5)
bladder calculi, urinary obstruction, diabetes mellitus, instrumentation, and immune deficiency
most common etiologic agents of cystitis
Escherichia coli, followed by Proteus, Klebsiella, and Enterobacter
result in emphysematous cystitis (gas-filled vesicles in the bladder wall)
Gas-forming bacteria (such as Clostridium perfringens)
Patients receiving systemic chemotherapy or pelvic irradiation may develop this type of cystitis
iatrogenic cystitis
Cytotoxic agents, such as cyclophosphamide, may cause this type of cystistis
hemorrhagic cystitis
this type of cystitis may occur following the irradiation of the bladder region
radiation cystitis
this type of cystitis is characterized by the presence of lymphoid follicles within the bladder mucosa and underlying wall
Follicular cystitis
this cystitis is manifested by infiltration of the submucosa by eosinophils, typically is a nonspecific subacute inflammation but may also be a manifestation of a systemic allergic disorder
Eosinophilic cystitis
All forms of cystitis are characterized by a triad of symptoms namely
frequency
lower abdominal, bladder region, or suprapubic pain
dysuria
an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with urinary tract symptoms of more than six weeks duration, in the absence of infection or other identifiable causes.
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
Typical cystoscopic findings include mucosal fissures and punctate hemorrhages (glomerulations). Microscopically, the pathologic findings are nonspecific; mast cells are often increased in the submucosa
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
main role of biopsy of interstitial cystitis
r/o carcinoma in situ
a distinctive chronic inflammatory reaction that appears to stem from acquired defects in phagocyte function that takes the form of soft yellow, slightly raised mucosal plaques, 3 to 4 cm in diameter
malakoplakia
common etiologic cause of cystisits including malakoplakia
E.coli
Characteristic feature of Malakoplakia which shows laminated mineralized concretions resulting from deposition of calcium in enlarged lysosomes
Michaelis-Gutmann bodies
an inflammatory lesion where the urothelium is thrown into broad bulbous polypoid projections as a result of marked submucosal edema
polypoid cystitis
lesions of the urinary bladder in which nests of urothelium (von Brunn nests) grow downward into the lamina propria. Here, epithelial cells in the center of the nest undergo metaplasia and take on a cuboidal or columnar appearance and are called ______ or retract to produce cystic spaces lined by flattened urothelium called and are called ______.
Cystitis glandularis, cystitis cystica
Cystitis glandularis and cystitis cystica often coexist, the condition is typically referred to as
cystitis cystica et glandularis
_____ is a precursor to bladder dysplastic lesions and in situ and invasive squamous cell carcinoma. Classically, this is seen in ______, a precursor to dysplastic lesions and in situ and invasive squamous cell carcinoma.
Extensive multifocal keratinizing squamous metaplasia, bladder schistosomiasis
Lesion where the overlying urothelium is focally replaced by cuboidal epithelium, which can assume a papillary growth pattern. Although the lesions are typically less than 1 cm in size, larger lesions have been reported that can produce signs and symptoms that raise a suspicion of cancer
nephrogenic adenoma
two distinct precursor lesions to invasive urothelial carcinoma
noninvasive papillary tumors
flat noninvasive urothelial carcinoma in situ
_______ is the most common precursor lesions of urothelial carcinoma and it originates from ______
noninvasive papillary tumors, papillary urothelial hyperplasia
major decrease in survival in bladder cancer is associated with
invasion of the muscularis propria
the most important risk factor for urothelial carcinoma, increasing the risk threefold to sevenfold,
Cigarette smoking
exposure to this industrial compound is a risk factor for urothelial carcinoma appearing 15-40 years after first exposure
aryl amines like 2-napthylamine
parasite infection in endemic areas that have an established risk for urothelial carcinoma
Schistosoma haematobium
T/F Long-term use of analgesics is implicated as a risk for urothelial CA
True
these are mutated in the pathway for tumor progression for non-invasive papillary utothelial cancer (3)
FGFR3, RAS, and PI3K
these mutations appear earlier in the pathway for flat urothelial CIS than in non-invasive papillary lesions
p53 and RB
These bladder tumors typically arise singly as small (0.5 to 2 cm), delicate structures superficially attached to the mucosa by a stalk and their individual finger-like papillae have a central core of loose fibrovascular tissue covered by epithelium that is histologically identical to normal urothelium and are referred to as
exophytic papillomas
are completely benign lesions consisting of inter-anastomosing cords of cytologically bland urothelium that extend down into the lamina propria; they simulate an invasive process
inverted papillomas
share many histologic features with papillomas, differing only in having thicker urothelium with greater density of cells
Papillary urothelial neoplasms of low malignant potential (PUNLMP)
invasive urothelial papillary tumor with an orderly architectural appearance and low-grade cytologic atypia.The cells are evenly spaced (i.e., maintain polarity) and cohesive.There are scattered hyperchromatic nuclei, infrequent mitotic figures predominantly toward the base, and slight variation in nuclear size and shape
Low-grade papillary urothelial carcinomas
invasive urothelial tumor with papillary architecture that contain dyscohesive cells with large hyperchromatic nuclei, irregular nuclear chromatin, and prominent nucleoli. Some of the tumor cells are highly anaplastic. Mitotic figures, including atypical ones, are frequent. Architecturally, there is disarray and loss of polarity
High-grade papillary urothelial carcinomas
is defined by the presence of cytologically malignant cells within a flat urothelium. It may range from full-thickness cytologic atypia to scattered malignant cells in an otherwise normal urothelium
CIS (or flat urothelial carcinoma)
most important prognostic factor in Invasive urothelial carcinoma
extent of spread (stage)
indication for radical cystectomy or radiation therapy with neoadjuvant or adjuvant chemotherapy
invasion of the muscularis propria layer
most common symptom of bladder cancer
painless hematuria
together referred to as non–muscle-invasive bladder tumors (2)
Noninvasive papillary urothelial tumors and those that solely invade the lamina propria
these tumors are treated with intravesical instillation of an attenuated strain of Mycobacterium bovis called bacillus Calmette-Guérin (BCG) (7)
CIS and papillary tumors that are large, hg, multifocal, hx of recurrence, or invade the lamina propria
CAP T staging
Ta
Tis
T1
T2a
T2b
T3a
T3b
T4a
T4b
Ta - noninvasive papillary ca
Tis - urothelial CIS, flat tumor
T1 - invades lamina propria
T2a - invade superfical muscularis propria (MP)
T2b - invades deep MP
T3a - inade perivesicular soft tissue microscopically
T3b - grossly
T4a - invades, protate, seminal v, uterus or vagina
T4b - pelvic or abdominal wall
In addition to muscle-invasive cancers, radical cystectomy is also indicated in cases of (3)
- CIS or hg pap CA refractory to BCG and other intravesical therapies
- CIS extending to prostatic urethra and ducts, sites where BCG can’t reach
- too large
T/F Mixed urothelial carcinoma with areas of squamous carcinoma is more frequent than pure squamous cell carcinoma.
True
most common benign mesenchymal tumor in the bladder
leiomyoma
The most common bladder sarcoma in adults is
leiomyosarcoma
The most common bladder sarcoma in infancy or childhood is
embryonal rhabdomyosarcoma (sarcoma botryoides)
most common cause of obstruction of the bladder outlet in males is
benign prostatic hyperplasia (BPH)
Urethritis is classically divided into
gonococcal and non-gonococcal causes
triad of arthritis, conjunctivitis, and urethritis
reactive arthritis (formerly Reiter syndrome)
cause of 25% to 60% of nongonococcal urethritis in men and about 20% in women
Various strains of Chlamydia (e.g., Chlamydia trachomatis)
an inflammatory lesion that presents as a small, red, painful mass about the external urethral meatus, typically in older females. It consists of inflamed granulation tissue covered by an intact but friable mucosa, which may ulcerate and bleed with the slightest trauma.
Urethral caruncle
cancerous lesions originating within the distal urethra are more often
squamous cell carcinomas and HPV-related
Malformation of the urethral groove and canal may create an abnormal opening either on the ventral surface of the penis (____) or on the dorsal surface (____)
hypospadias, epispadias
When the orifice of the prepuce is too small to permit its normal retraction, the condition is designated____
phimosis
most frequent penile neoplasms (2)
squamous cell carcinoma and benign genital warts
characterized by hard penile plaques that result from the deposition of collagen in the connective tissue between the corpora cavernosa and the tunica albuginea
Peyronie Disease
non–HPV-related (differentiated) penile intraepithelial noeplasia (PeIN) is associated with
balanitis xerotica obliterans
Undifferentiated PeIN is composed of more overtly malignant cells and may manifest clinically as two distinct lesions
Bowen disease and bowenoid papulosis
most commonly affects the penile shaft and scrotum of older men. At these sites, it appears as a solitary, thickened, gray-white, opaque plaque. In less common cases when it affects the glans, the lesion acquires a velvety red appearance. Histologically, the lesion consists of dysplastic squamous cells containing large hyperchromatic irregular nuclei and lacking orderly maturation. Mitoses, some atypical, are numerous
Bowen disease
Undiff PeIN that occurs in sexually active younger adults. It presentation as multiple (rather than solitary) reddish brown papular lesions. It is etiologically related to HPV 16
Bowenoid papulosis
Undiff PeIN that virtually never develops into invasive carcinoma and usually regresses spontaneously
Bowenoid papulosis
T/F Circumcision confers protection from penile invasive squamous cell carcinoma
true
Squamous cell carcinoma of the penis usually originates in
glans or inner surface of the prepuce near the coronal sulcus
is a complete or partial failure of the intra-abdominal testes to descend into the scrotal sac and is associated with testicular dysfunction and an increased risk of testicular cancer
Cryptorchidism
Testicular descent occurs in two phases namely
transabdominal phase
inguinoscrotal phase
transabdominal phase is controlled by what hormone?
müllerian-inhibiting substance
inguinoscrotal phase is dependent on what hormone
androgen
most common site of arrest in cryptorchidism
inguinal canal
earliest histologic change in cryptorchidism
thickening of the basement membrane
T/F repositioning of testis in cryptorchidism has been proven to completely eliminate the risk of cancer
false
The cryptorchid testis carries a ______fold higher risk for testicular cancer
3-5
tuberculosis and gonorrhea, arise first in the epididymis and only involve the testis secondarily, while others, such as _____, involve the testis first
syphilis
epididymitis in childhood is usually associated with______ and infection with ________.
a congenital genitourinary abnormality, gram-negative rods.
In sexually active men younger than age 35 years most common causes of epididymitis are (2)
C. trachomatis and Neisseria gonorrhoeae
In men older than age 35 the more commone causes of epididymitis are
E. coli and Pseudomonas
Histologically, this type of orchitis is distinguished by granulomas restricted to spermatic tubules
granulomatous autoimmune orchitis
T/F testicular involvement in mumps is more common in school-age children rather than post pubertal males
false, more common in postpubertal
The morphologic pattern of the reaction in testicular syphilis takes two forms
1) obliterative endarteritis associated with perivascular cuffs of lymphocytes and plasma cells (2) granulomatous inflammation, a lesion known as a gumma.
histologic hallmark of testicular syphilis
obliterative endarteritis associated with perivascular cuffs of lymphocytes and plasma cells
In (children/adults?) torsion results from a bilateral anatomic defect that leads to increased mobility of the testes called _____
adults, bell-clapper abnormality
The most common benign paratesticular tumor is
adenomatoid tumor
The most common malignant paratesticular tumors are ____ in children and ____ in adults.
rhabdomyosarcoma, lipsarcoma
most common cancer in the 15-45 age group
germ cell tumors
Components of this syndrome include cryptorchidism, hypospadias, and poor sperm quality
testicular dysgenesis syndrome
this syndrome is associated with a greatly increased risk (50 times normal) for development of mediastinal GCTs, but these patients do not develop testicular tumors
Klinefelter syndrome
genetic loci linked to familial GCT risk (2)
KIT and BAK
___ mutation is involved in the genesis of precursor lesion germ cell neoplasia in situ (GCNIS)
KIT
Progression to full-blown GCTs is strongly associated with ______ a cytogenetic alteration that is invariably found in invasive GCTs regardless of histologic type
isochromosome 12p, a reduplication of the short arm of chromosome 12
is the most common type of GCT
seminoma
GCT composed of sheets of uniform cells divided into poorly demarcated lobules by delicate fibrous septa containing a lymphocytic infiltrate, The cell is round to polyhedral and has a distinct cell membrane; clear or watery-appearing cytoplasm; and a large, central nucleus with one or two prominent nucleoli
seminoma
affected individuals are generally older
seminoma or spermatocytic tumor?
spermatocytic tumor
seminoma and other GCNIS tumors are associated with this cytogenetic alteration _______, while spermatocytic tumors are associated with ____
isochromosome 12p, chromosome 9q
________ are notably lacking in the morphology of spermatocytic tumor vs seminoma and is also OCT3/4____
inflammatory infiltrates, negative
Germ cell tumor with neoplastic cells that have an epithelial appearance, are large and anaplastic, and have hyperchromatic nuclei with prominent nucleoli. The cell borders are usually indistinct, and there is considerable variation in cell and nuclear size and shape (pleomorphism). Mitotic figures and tumor giant cells are frequently seen.Vascular-lymphatic invasion is common
embryonal carcinoma
ihc for embryonal carcinoma
oct3/4+, cd30+, cd117-
most common testicular tumor in infants and children up to 3 years of age
prepubertal yolk sac tumors
germ cell tumor composed of a lace-like (reticular) network of medium-sized cuboidal, flattened, or spindled cells. Eosinophilic, hyaline-like globules containing α-fetoprotein (AFP) and α1-antitrypsin are also typically seen
yolk sac tumor
Yolk Sac Tumor is also known as ___ and in approximately 50% of tumors, structures resembling endodermal sinuses called ____ may be seen
endodermal sinus tumor, Schiller-Duval bodies
ihc for yolk sac tumor
sall4+ oct3/4- cd30- glypican3+
most aggresive GCT
choriocarcinoma
malignant non–germ cell (somatic) tumors arise in postpubertal teratomas, a phenomenon referred to as ___. tumor.These non–germ cell malignancies retain isochromosome ___
teratoma with somatic-type malignant transformation, 12p
the standard management of a solid testicular mass is
radical orchiectomy
characteristic mode of spread of testicular tumors
Lymphatic spread
serum biomoarker in germ cell tumors which correlates with the mass of tumor cells and provides a tool to assess tumor burden
LDH
Both of these markers are elevated in more than 80% of individuals with nonseminomatous GCTs at the time of diagnosis
AFP and hCG
Pure choriocarcinoma and mixed GCT with predominantly choriocarcinoma. prognosis?
poor
is radiosensitive and chemosensitive, has the best prognosis among testicular gcts
seminoma
Cells of this sex cord stromal tumor elaborate androgens and in some cases estrogens and corticosteroids as well. They may arise in children or adults. As with other testicular tumors, the most common presenting feature is testicular swelling, but in some patients gynecomastia brings them to clinical attention.
Leydig cell tumor
The cytoplasm of leydig tumors frequently contains lipid droplets, vacuoles, or lipofuscin pigment and, most characteristically, rod-shaped _____
crystalloids of Reinke
hormonically silent sex cord-gonadal tumor
sertoli cell tumors
Histologically, the tumor cells of this sex cord tumor are arranged in distinctive trabeculae that tend to form cord-like structures and tubules
sertoli-cell tumors
most common form of testicular neoplasm in men older than 60 years of age
Primary testicular lymphomas
The most common testicular lymphomas, in decreasing order of frequency (3)
dlbcl
burkitt lymphoma
Epstein-Barr virus–positive extranodal NK/T-cell lymphoma
a mesothelial-lined surface exterior to the testis
tunica vaginalis
accumulation of serous fluid ni the tunica vaginalis
hydrocele
a collection of blood in the tunica vaginalis. It is an uncommon condition usually encountered following testicular trauma or torsion, or in individuals with systemic bleeding disorders
hematocele
refers to the accumulation of lymph in the tunica and is almost always found in patients with elephantiasis who have widespread, severe lymphatic obstruction caused, for example, by filariasis
Chylocele
refers to a small cystic accumulation of semen in dilated efferent ducts or ducts of the rete testis
Spermatocele
a dilated vein in the spermatic cord
Varicocele
In a normal adult, the prostate weighs approximately ___ grams
20
the prostate can be divided into four biologically and anatomically distinct regions
peripheral, central, transition, and periurethral zones
Most prostatic carcinomas arise from the ____ zone
peripheral
BPH arises from _____ zone
transitional
most cases of acute prostatitis are caused by various strains of
E. coli
Biopsy of a gland in which acute prostatitis is suspected is contraindicated, as this may lead to
sepsis
Diagnosis of chronic bacterial prostatitis depends on
demonstration of leukocytosis in expressed prostatic secretions and positive bacterial cultures
most common form of prostatitis
Chronic abacterial prostatitis
in chronic abacterial prostatitis, e xpressed prostatic secretions contain _____ leukocytes per high-power field, and bacterial cultures are uniformly ____
> 10, negative
the most common cause of Granulomatous prostatitis in the US
instillation of BCG for treatment of bladder cancer
the most common benign prostatic disease in men older than age 50 years
bph
activates androgen receptors (AR) in BPH
dihydrotestosterone (DHT)
androgen receptors (AR) translocate from the cytoplasm to the nucleus and activate the transcription of androgen-dependent genes, which encode several growth factors and their receptors. Most important among the upregulated factors are members of the (2)
fibroblast growth factor (FGF) and trasforming growth factor B (TGFB)
____ serves as a mitogen for fibroblasts and other mesenchymal cells but inhibits epithelial proliferatio, while ____, produced by stromal cells, are paracrine regulators of androgen-stimulated epithelial growth
TGF B and FGF
besides androgens, ______ contribute to BPH pathogenesis by tipping the balance toward proliferation
estrogens
In treatment of symptomatic bph, the ______ decrease prostate smooth muscle tone, while the _______ physically shrink the prostate by decreasing DHT synthesis
α-adrenergic blockers and 5α-reductase inhibitors
second cause of cancer-related death in men
prostate cancer
polymorphisms in _______, an enzyme involved in detoxification of polycyclic aromatic hydrocarbons, are linked to prostate cancer risk
glutathione-S-transferase (GSTP1)
modest increase in risk of prostate CA are variants in regulatory regions that influence the expression of (4)
MYC
BRCA2
MMR
HOXB13
the growth and survival of prostate cancer cells depend on
androgens
The most common genetic alteration in the prostate is
chromosomal rearrangement of ETS family transcription factor gene (most commonly ERG or ETV1) next to the androgen-regulated TMPRSS2 promoter
One particularly frequent early event in prostate cancer is epigenetic silencing by DNA methylation of the
GSTP1
pathognomonic features of prostate cancer
PNI
glomerulation
mucinous fibroplasia
are the most important prognostic factors in prostate cancer
Grade and stage
Prostate cancers that reveal abundant mucinous secretions in greater than 25% of the tumor are termed
colloid carcinoma of the prostate
The most aggressive variant of prostate cancer
small-cell carcinoma (also known as neuroendocrine carcinoma)
The most common tumor to secondarily involve the prostate is
urothelial cancer
