Chapter 20, Part Of Others Flashcards
Urothelium
Special form of transitional epithelium
-5-6 layers of cells with oval nuclei, often with linear nuclear grooves, and a surface layer consisting of large, flattened umbrella cells with abundant cytoplasm
Morphology lamina propria of bladder
Wisps of smooth muscle that form discontinuous muscularis mucosae
Muscularis proporia
Deeper well defined larger muscle bundles of detruser muscles
Bladder cancers are staged on the basis of invasion of detruser muscle
What are the 3 points of narrowing of the ureter
Uteropelvic junction
Where the ureter enters the bladder
Where ureter crosses the iliac vessels
How does the ureter enter the bladder
Obliquity of the intramural segment of the urethral orifice permits the enclosing bladder msuculature to act like a sphincteric valve, blocking the upward reflux of urine even in the presence of marked distention of the urinary bladder
Defects in the and of the ureter entering the bladder may predispose to what
VUR->pyelonephritis
Double birdie ureters
Come off double renal pelvis or bifid pelvis
Most are unilateral and no clinical significance
Ureteropelvic junction obstruction
Most common cause of hydronephrosis in infants and kids
Early cases are more likely to be bilateral and happen in males
-often associated with other congenital abnormalities (espicially agenesis of the other kidney)
In adults, more common in girls and unilateral
-due to abnormal smooth muscle bundles at the UPK
Diverticula
Saccular outpouchings of the urethral wall
Most are asymptomatic, but urinary stasis can sometimes lead to recurrent infections
Can be associated with: dilation (hydroureter), elongation, and tortuosite of the ureters
Urethritis
Inflammation
Actually not associated with infections, little clinical significance
Primary tumor of the ureter are __
Rare
Small benign tumors of the ureter are generally of ___ origin in ureter
Mesenchymal
Fibroepithelial polyp ureter
Tumor like lesion that presents as a small mass projecting into the lumen
Often in kids
May also occur in the bladder, renal pelvises and urethra
Polyp is composed of loose, vascularized CT overlaid by urothelium
Primary malignant tumor of ureter: most common?
Urothelial carcinoma
Screening for cancer with urinary cytology is diagnostic for ureter?
No
Renal pelvic carcinoma, bladder malignancy, urethral carcinoma==all urothelial tissue
Field effect, field cancerization—the urine with carcinogens baths all this tissue
When do people get primary malignant tumors of ureter
50-60
What do primary malignant tumors of the ureters cause cause
Hydronephrosis
Describe primary malignant tumor of ureter
Sometimes multifocal and commonly occur with similar neoplasms in the bladder or renal pelvic
Sclerosing retroperitoneal fibrosis in ureter
Obstructive lesion, fibrotic proliferative inflammatory process encasing the retroperitoneal structures (SAD PUCKERS) and causing hydronephrosis
Most idiopathic/primary (ormond disease)
Who gets sclerosing retroperitoneal fibrosis
Middle late age men associated with IgG4 related diseases sometimes
Sclerosing retroperitoneal fibrosis involves other tissues as well, particularly what
Exocrine organs such as the pancreas and salivary glands
What can cause sclerosing retroperitoneal fibrosis
Drugs-ergot derivatives, beta adrenergic blockers
Adjacent inflammatory process—vasculitis, diverticulitis, IBD
Malignant disease—lymphomas, urinary tract carcinomas
LM sclerosing retroperitoneal fibrosis
Fibrous tissue containing prominent infiltrate of lymphocytes, often with germinal centers, plasma cells (IgG4 positive) and eosinophils
Treat sclerosing retroperitoneal fibrosis
Corticosteroids, but will need stents or surgery (ureterolysis: extrication of the ureters form the surrounding fibrous tissue)
Urinary bladder
Ok
Vesicourectal reflux
Most common and serious congenital anomaly of bladder
Contributes to renal infections and scarring ->pyelonephritis
Urinary bladder diverticula
Pouchlike evaginations of the bladder wall
Congenital or acquired (prostatic enlargement)
Often due to increase intravesical pressure
Urinary stasis predisposes patients to infection and formation of bladder calculi
What does bladder diverticula predispose to
VUR
Advanced carcinoma as a result of the thin or absent muscle wall of diverticula
Exstrophy of bladder
Developmental failure of the anterior abdominal wall
Bladder communicates directly with overlying skin or is exposed sac
Issue with exstrophy of bladder
Exposure of bladder mucosa may undergo colonic glandular metaplasia and is subject to infections
Increased risk of adenocarcinoma and infections that spread to upper levels of the urinary system
Treat exstrophy of bladder
Surgical correction=long term survival
Patent urachus
Totally patent: fistulas urinary tract
Rachael cyst
Only the center is patent and is lined by urothelium or metaplastic glandular epithelium
Rarely do the cysts turn into cancer
Cystitis (acute or chronic)
Infections in the urinary bladder have retrograde spread of bugs into the kidneys and collecting systems
What causes cystitis infections
E. coli
Proteus, klebsiella, enterobacter
Chlamydia, mycoplasma,
Tuberculous cystitis
-almost always a sequel to renal tuberculosis
Candida/cryptococci
Schistosoma (Egypt)
Chlamydia, mycoplasma, adenovirus
Predisposition to cystitis
Bladder calculi
Urinary obstruction
Diabetes mellitus
Instrumentation
Immune defiency
Irradiation of the bladder
Morphology acute cystitis
Hypermedia of the mucosa and neutrophilic infiltrate (sometimes with exudate)
-patients receiving cytotoxic anti tumor drugs or infected with adenovirus can develop hemorrhagic cystitis
Chronic cystitis morphology
From chronic bacterial infection associated with mononuclear cells
Follicular cystitis: presence of lymphoid follicles within the bladder mucosa and underlying wall, not always related to infection
Eosinophilic cystitis: infiltration of eosinophils into the submucosa; not always related to infection
Clinical cystitis
Frequency (every 15-20 min)
Lower abdominal pain, localized over the bladder region/suprapubic region
Dysuria (pain burning)
Interstitial cystitis (chronic pelvic pain syndrom)
Chronic cystitis, usually female
Pain and dysuria in absence of infection
Early and late phase interstitial cystitis
Early-punctuate hemorrhages
Late/classic/ulcerative phase-chronic mucosal ulcer (hunger ulcers) with inflammation and transmural fibrosis leading to a contracted bladder
Morphology interstitial cystitis
Increased mucosal mast cells
Biopsy to rule out carcinoma in situ!!
Malakoplakia
Chronic bacterial cystitis (e coli or proteus)
Acquired defect of phagocyte function
Who gets malakoplakia
Immunocompromised
Morphology malakoplakia
3-4 cm soft, yellow, mucosal plaques with foamy macrophages
Macrophages with abundant granular PAS positive cytoplasm
Michaelis-Guzman bodies: macrophages with intra-lysosomal laminated calcified concretions
Macrophages become overloaded with undirected bacterial products and become giant
Polypoid cystitis
Inflammatory lesion from irritation of bladder mucosa
Most commonly due to indwelling catheters, but can be due to any injurious agent
Morphology polypoid cystitis
Marked submucosal edema—>broad bulbous polypoid projections
Confused with papillary urothelial carcinoma both clinically and histologically
Cystitis glandularis and cystitis cystica
Metaplastic lesions seen in normal bladders or chronic cystitis
Morphology cystitis glandularis and cystitis cystica
Nests of transitional epithelium (brunn nests) grow downward into lamina proporia
Nests transform into cuboidal or columnar epithelium (glandularis )
These conditions occur together often and is called cystitis cystica et glandularis
Flattened cells lining fluid filled cysts
Squamous metaplasia
Response to injury
Urothelium replaced by non keratinize game squamous epithelium
Should be distinguished from glycosylated squamous epithelium that is normally found in women at the trigone
Nephrogenic adenoma (benign)
She’d tubular cells implant and proliferate at sites of injured urothelium
Urothelium turns into cuboidal epithelium that assumes a papillary growth pattern
Possible extends into superficial detruser muscle and mimics a malignant process (still benign)
Bladder neoplasm
95% of bladder cancer are of epithelial origin
Called urothelial or transitional tumors
Remaining cancers are mesenchymal
Urothelial tumors
90% of all bladder tumors
-may arise anywhere there is urothelium (renal pelvis to distal urethra)
Small benign lesions to aggressive cancers
Often multifocal at presentation
What are the two distinct precursor lesions or urothelial tumors
Noninvasive papillary tumors (most)
Flat noninvasive urothelial carcinoma
Non invasive papillary tumors
Most common precursor lesion to urothelial tumors
Originates from papillary urothelial hyperplasia
Lesions range in atypia that reflects biological behavior
Carcinoma in situ
Term used to describe high grade epithelial lesions that have the cytology features of malignant cells but are confined to the epithelium but show no evidence of basement membrane invasion
High grade lesions
Invasive bladder cancer
The high grade invasive component destroys the precursor lesion
Typically appears as a large, ulcerated mass
Invasion into the LP worsens prognosis, but invasion into the muscularis propria is major factor for survival
Risk factors for urothelial carcinoma
Male 50-80 CIGARETTE (50-80%) -cigars, pipes, and smokeless tobacco less Industrial exposure to aryl amines -15-40 years after exposure
Schistosoma haematobium
-Egypt Sudan
Long term use of analgesics
Heavy exposure to cyclophosphamide (immunosuppressive)
-also induces hemorrhagic sytitis
Irradiation of other pelvic malignancy
-bladder cancers occur many years after
Genetic alterations of urothelial carcinoma leading to constitutive activation of growth factors receptor signaling cascades
FGFR3 (receptor tyrosine kinase)
TP53 and RB
HRAS
Loss of 9p
FGFR3 urothelial carcinoma
Gain of function mutation; oncogene
Non invasive, low grade papillary carcinomas
TP53 and RB
Loss of function mutation ; tumor suppressor
Almost always seen in high grade and muscle invasive tumors
HRAS uretheliocarcinoma
Gain of function mutation; oncogene
Low grade non invasive tumors
HRAS and FGFR3 are generally mutually exclusive in bladder cancer bc RAS signal transducers act downstream of receptor tyrosinase kinases
Loss of chromosome 9p urothelium carcinoma
Specifically loss of CDKN2A (p16/INK4 and ARF) tumor suppressor gene
Often the only abnormality seen in superficial non invasive papillary tumors and occasionally in non invasive flat tumors
Mostmorphology urothelial tumors
Most arise from the lateral and posterior walls at bladder base
Papillary lesions are red and elevated
Multiple, discrete tumors are often present
Overall majority of papillary tumors are low grade
-encompass a range from benign papilloma to highly aggressive anaplastic cancer
Papillomas
Rare bladder cancer found in young
Exophytic papilloma grow out
Histology papillomas
Arise singly as a delicate urothelium cover over finger like papillae with a loose fibromuscular core histologically identical to normal urothelium
Superficially attached to the mucosa by stalk (pedunculated)
Extremely low incidence of progression or recurrence—benign
Inverted papilloma (benign)
Inter anastomoses cords of bland urothelium extending into the LP
Papillary urothelial neoplasms of low malignant potential (PUNLMP)
Share many histologically features with papilloma , except:
- slightly larger than papillomas
- thicker urothelium
Rarely progress to higher grade—doesn’t mean they don’t
Looks bad but the pathologist doesn’t think it looks like a malignancy
Low grade papillary urothelial carcinomas
Orderly cytology and architecture
Minimal atypia
Rarely invade
Rarely fatal
High grade papillary urothelial cancer
Discohesive cells with anaplastic features
- architectural disarray, loss of polarity
- large, hyperchromatic nuclei
- atypical mitosis figures
High grade papillary urothelial cancer has high risk of what
Invasion into the muscular layer, higher risk of progression and significant metastatic potential
Metastases or urothelial tumors of the bladder
Adjacent structure invasion
Fistulas communications with vagina or rectum
40% to regional LNs
Hematogenous spread to liver, lungs, bone
Carcinoma in situ (flat urothelial carcinoma)
Cytogically malignant cells within a flat urothelium
Can range from full thickness atypia to scattered malignant cells in an otherwise normal urothelium (pagetoid spread)
Morphology carcinoma in situ
Lack of cohesiveness leads to shedding of malignant cells into urine
-when extensive , only a few CIS cells may be left clinging to a largely denuded BM
Appears as an area of mucosal reddening, granularity, or thickening, but no mass projecting into the lumen-flat
No evident intraluminal mass
Multifocal
Flat urothelial lesions are always carcinoma in situ
If untreated what percent of CIS will invade
50-75%
Invasive urothelial cancer is associated with what
Papillary urothelial cancer, high grade or adjacent CIS
Invasion of muscularis mucosae (detruser) is prognostically important
Biopsy understating is a problem-staging at the initial diagnosis is the most important factor in determining the outlook for the patient
-extend of spread=staging
Squamous cell carcinoma of the bladder
Increased incidence in countries with endemic schistosomiasis-middle east
-only place; very unusual in the US
Associated with chronic bladder irritation and infection
Mixed urothelial carcinoma with areas of squamous carcinoma of the bladder
Invasive, fungating and/or infiltrating and ulcerations tumors
More common that purely squamous cell bladder cancers
Can be well differentiated or anaplastic
Adenocarcinoma of the bladder
Rare
Histologically identical to adenocarcinomas seen in GI tract
Some arise from Rachael remnants or in the setting of intestinal metaplasia
Small cell carcinoma of the bladder
Indistinguishable from small cells arcinoma of the lungs
Often associated with urothelial, squamous adenocarcinoma
Bladder cancer presntation
Painless hematuria
Frequency, urgency, dysuria
Pyelonephritis or hydronephrosis may follow if the urethral orifice is involved
Tend to recur after excision at a higher grade in different sites
Prognosis bladder cancer
Papillomas or low grade papillary urothelial cancer have 98% 10 year survival rate
Less than 10% progress to a higher grade lesion, but if they do 25% of those patients expire
Patients with primary carcinoma in site are less likely to progress to muscle invasive cancer as compared to carcinoma in situ associated with infiltrating urothelial carcinoma
Urothelial carcinoma has a 30% chance of being fatal if it invades the LP but otherwise squamous cell carcinoma and adenoacarcinoma are associated with worst prognosis
Treat bladder cancer: small, localized low grade papillary tumors
Diagnostic transurethral resection; follow with cystoscope and urine cytology
Treat bladder cancer : patients at high risk for recurrence==intra vesical instillation of an attenuated strain of mycobacterium Boris BCG
Bacterial elicit a local inflammatory reactions hat destroys the tumor
Radical cystectomy reserved for really advanced cancers
Treat bladder cancer: advanced
Radical cystectomy
How cure bladder cancer
Respond well to chemo, but need surgery to cure
Mesenchymal tumors of the bladder
Benign tumors
Rare but most common are leiomyomas
They grow as isolated, intramural , encapsulated, oval to spherical masses
Sarcomas of bladder
Uncommon
Produce large masses that grow into the vesicle lumen
Have soft grey white appearance
What sarcoma most common in kids
Embryonal rhabdomyosarcoma, can grow into a grape like mass (sarcoma botryoides)
Most common sarcoma in adults
Leiomyosarcoma
Secondary tumors
From direct extension from primary lesion in nearby structure (cervic, uterus, prostate, rectum)
Obstruction
Males or femelas?
Prostate enlargement
Obstruction of bladder in men due to nodular hyperplasia
Cystocele of bladder
Most common obstrucion in females
Morphology of obstruction
The bladder wall continues to thicken
With time, the wall can be so thick that crypt and eventually diverticula will form
The bladder can become very enlarged and thinned in some cases where the bladder can reach to the brim of the pelvis or to the umbilicus
Urethra
Ok
Urethritis
Gonococcal or nongonoccal
Conococcal urethritis
Early manifestations of neisseria gonorrhea infection (gram - diplodocus)
Often have a more pursuant discharge
No gonococcal urethritis
Most commonly caused by chlamydia trachmoatis (gram - , ovoid, and nonmotile)
-more serous discharge
A-C serotypes of nongonococcal urethritis
Leading cause of blindness in the world
Cause trachoma
D-K serotypes of nongonococcal
The GU tract one; cause urethritis, pelvic inflammatory disease, ectopic pregnancy, neonatal pneumonia, and neonatal conjunctivitis
L1, 2, 3, nongonoccocal
Lymphogranuloma venereum (painless lesion
Chancre is painful
What else can cause nongonoccal urethritis
Mycoplasma
What is urethritis associated with in women and men
Cystitis women
Prostatitis men
Clinical urethritis
Local pain, itching, urinary frequency
May warn of more serious problems that are further up the tract
Urethral carbuncle
Painful, small, red inflammatory lesion of the external urethral meatus in (older) females
Granulation tissue with friable mucosa covering
Bleed easily due to ulceration
Treat urethral caruncle
Excision is curative
Primary carcinoma of the urethra: proximal urethra
Show urothelial differentiation and are just like ones in the bladder
Primary carcinoma: distal urethra
More commonly squamous cell carcinoma
___ carcinomas are uncommon in the urethra, but occur in women when they appear
Adeno
Hypospadias
Urethral opening on the ventral aspect of the penis
More common than epispadias
Epispadias
Urethral opening not he dorsal surface of the penis
Less common
What are hypospadias and epispadias associated with
Abnormalities of normal descent of the testes and comorbid with other malformations of the urinary tract
Problem with hypospadias and epispadias
Abnormal openings are often constricted and lead to obstruction of urine
If the openings are located near the base of the penis, ejaculation/insemination may be hindered
Phimosis
Prepuce orifice is too small to permit normal retraction
Why get phimosis
Developmental causes are less common than secondary to inflammation that cause scarring of the preputial ring
Predisposition to secondary infections and even carcinoma
Balanoposthitis
Infection of the glans and prepuce by non specific organisms (not STD)
What organisms cause balanoposthitis
Candida albicans
Anaerobic bacteria
Gardnerella
Pyogenic bacteria
How does balanoposthitis
Poor local hygiene in uncircumscribed males->smegma accumulation->inflammatory scarring->phimosis
Condyloma acumunita (penile tumor)
Benign sexually transmitted wart
HPV 6>11
-gardasil==HPV 6,11,16, and 18
Single of multiple sessile or pedunculated, red papillary excrescences
Condyloma recurrence
Recurs after excision, but rarely transforms to malignancy
Where is a condyloma acuminata
At coronal sulcus or inner prepuce
Acanthosis with condyloma acuminata
Superficial hyperkeratosis and thickening of the underlying epidermis
-branching, villous, papillary CT stroma is covered by orderly, hyperplastic stratified squamous epithelium
Koliocytosis condyloma acuminata
Cytoplasmic vacuolization of the squamous cells; characteristic of HPV
Peyronie disease
Benign proliferation of fibroblasts
Results in fibrous bands involving the penile corpus cavernous
Causes penile curvature and pain during intercourse
Malignant tumors now
Ok
Carcinoma in situ
Malignant tumors
Strongly associated with HPV 16
-gardasil 6, 11, 16, 18
What are the two types of carcinoma in situ
Bowen and bowenoid
Bowen disease who gets it
Male of female >35
Morphology Bowen
Solitary thickened, gray white plaques over penile shaft or red shiny lesions on the glans and prepuce
Epidermis I’d hyperproliferative, lots of mitosis, some atypia, dysplasia, no orderly maturation
Hyperchromatic nuclei
Intact BM, but 10% can turn into invasive squamous carcinoma
-Bowen disease will transform into infiltrating squamous cell carcinoma in 10% of patients over a span of many years
Bowenoid papulosis who gets
Younger, sexually alive adult patients
Morphology bowenoid papulosis
Multiple, pigmented popular lesions on external genitalia
Multiple (instead of solitary) reddish brown popular lesions
Clinical bowenoid
Frequently spontaneously regress
Rarely evolve to invasive carcinoma
Clinical Bowen
Will transform into infiltrating squamous cell carcinoma in 10% of patients over a span of many years
Histology of Bowen and bowenoid papulosis are __-
Indistinguishable
How differentiate Bowen from bowenoid
Age and number of lesions
Bowen->35 , solitary lesion-invade in 10% over many years
Bowenoid-younger, multiple-rarely evolves to invasive carcinoma
Squamous cell carcinoma of the penis is associated with what
Poor genital hygiene+high risk HPV infection (gardasil 6, 11, 16, 18)
40-70
Where is squamous cell carcinoma of the penis common
<1% of male cancer, but can account for a lot more in Asia, Africa, and South America
Regions that don’t circumcise:higher prevelance due to smegma accumulation under foreskin
Circumcision is ___ for squamous cell carcinoma fo the penis
Protective —-rare in Muslims and jews
Which HPV most commonly causes squamous cell carcinoma of the penis
6, 11, 16, 18
What lifestyle factor is a huge risk for squamous cell carcinoma of the penis
Smoking
Morphology squamous cell carcinoma of the penis: flat pattern
Epithelial thickening on the glans or inner surface of the prepuce
Progresses to an ulcerated papule
Morphology squamous cell carcinoma of the penis :papillary
Epithelial thickening with graying and fissuring of the mucosal surface
Stimulated condyloma acuminata and may produce a cauliflower like fungating mass
Morphology squamous cell arcinoma of the penis :verrucous carcinoma
Uncommon
Exophytic, well differentiated variant of squamous cell carcinoma
Locally invasive; rarely metastasizes
Squamous cell carcinoma of the penis is __ growing and ___ invasive
Slow
Locally
Presntation of squamous cell carcinoma of the penis
For a year of more before brought to medical attention
Not painful until they secondarily ulcerate and become infected
Where does squamous cell carcinoma of the penis metasticize to
Regional (inguinal and iliac nodes), distant is uncommon until far advances
Prognosis squamous cell carcinoma of the penis
50% of men contain cancer in their enlarged inguinal nodes-
5 year survival based on stage
66% if confined
27% with lymph node involvement
What is the most commmon congenital anomaly of the testes
Cryptorchisdism
Cryptorchidism : what is it and what is problem
Failure of testis descent =tubular atrophy and sterility
75% unilateral
1% of 1 year old boys
Usually isolated anomaly
Increased risk testical germ cell tumors
Morphology cryptorchordism
Decreased germ cell development, thickening and hyalinization of seminiferous tubule basement membrane
Fibrosis with sparing of prominent leydig cells
Clinical cryptorchidism
Completely asymptomatic and comes to attention when the scrotal sac is discovered to be empty by the patient or examining physician
Why does concomitant inguinal hernia accompany
When testis lie in inguinal canal, it is more prone to trauma and crushing injuries
What are undeserved testes a risk for
Testicular cancer
Treat cryptorchidism
Most will descend on their own by 1 but will need surgery before 2 if not
If uncorrected cryptorchidism testicle may develop
Inflammation is more commmon in the ___ than the ___
Epididymis
Testis
Epididymis first, then to tests
Gonorrhea
TB
Testis then to epididymis (exception)
Syphilis
Epididymis is commonly spared altogether
Nonspecific epiddiymitis and orchiitis
Due to UTI reaching the epididymis via vas deferens or spermatic cord lymphatics
Childhood cause of nonspecific epididymitis and orchitis
Congenital or gram negative rods
Sexually active <35 cause of nonspecific epididymitis and orchitis
Chlamydia trachomatis, neisseria gonorrhea
Cause of nonspecific epiddymitis and orchitis in men>35
Common UTI agents (E coli, pseudomonas)
Morphology nonspecific epididymitis and orchitis
Nonspecific congestion, edema and neutrophilic, macrophage and lymphocyte infiltrates
Can progress to abscess formation and complete suppurative necrosis of the entire epididymis
Sterilize due to infalmmmation testis by traveling through the epididymis leading to fibrous scarring of both
Local lymphatics channels
Leydig cells less affected, thus testosterone levels generally maintained
Granulomatous (autoimmune) orchitis
Painless moderately tender testicular mass of sudden onset sometimes associated with fever in middle aged people
Can loops like tubercles,but is found diffusely throughout the testis
Granulomatous orchitis is restricted to where
Spermatic tubules
Gonorrhea
Retrograde expansion of infection from posterior urethra to prostate, seminal vesicles and epididymis
- ascending infection
- from neglected gonococcal infection
Severe gonorrhea
Epiidymal abscess==destruction and scarring
Untreated gonorrhea
Testis suppurative orchitis
Mumps
Systemic viral infection
Commonly affects children, though testicular involvement at this age is rare
20-30% or post pubertal men who are infected present with orchitis 1 week after inflammation of parotid glands
Tuberculosis
Begins in the epididymis
Secondary testis involvement
Caseating granulomas with histology identical to granulomas elsewhere in the body
Syphilis
Congenital or acquired
Testes are involved first and the epididymis is commonly spared
What are the two different morph pattterns of symphysis
Nodular gummas
Diffuse interstitial inflammation that produces the histologic hallmark of syphilitic infections, obliterating endarteritis associated with perivascular cuffs of lymphocytes and plasma cells
Torsion
Twisting of the spermatic cord cuts off testicular venous drainage
Neonatal torsion
Occurs in utero or shortly after birth, not associated with congenital anomaly
Adult torsion
Adolescence, occcurs without prior injury, even during sleep
Comes from an anatomical defect (bell clapper abnormality) that leads to increased mobility of the testes
Orchiopexy performed bilaterally to prevent similar fate in contralateral testis
Problem with torsion
Vascular engorgement with potential for hemorrhagic infarct
Arterial supply remains patent-torsion occluded the venous outflow (thinner wall, less pressure, more compressible)
Treat torsion
UROLOGIC EMERGENCY, without treatment testes enlarge, soften, necrosis, and hemorrhagic
-leads to testicular infarction
Surgery<6 hours can preserve testicular viability
Lipoma
Lesions that involve the proximal spermatic cord
Fat around the cord may represent retroperitoneal adipose tissue pulled into the inguinal canal with a hernia sac rather than a true neoplasm
-identified at the time of inguinal hernia repair
Adenomatoid tumor
Most common benign paratesticular neoplasm
Small nodules of mesothelioma cells near the upper epidydimal pole
-not mesothelioma
Well circumscribed
LM adenomatoid tumor
Minimal invasion into adjacent testis
If an adenomatoid tumor is identified as benign intraoperatively the surgeon should do what
Can spare the patient and orchid to my and locally excise the tumor
Rhabdomyosarcoma
Most common paratesticular tumor in kids
Liposarcoma
Most common paratesticular tumor in adults
Testicular tumors now
Ok
Germ cell tumors (95% of testicular tumors)
Malignant
Most common malignancy in men 15-34
Two types of germ cell testicular tumors
Seminomas and nonseminomas
White:black ration for testicular tumors
5:1
Sex cord stromal tumors (5% o testicular tumors)
Generally benign testicular tumor
Environmental risk factors of testicular germ cell tumors
Testicular dysgenesiis syndrome
Klinefelters syndroem XXY
Testicular dysgenesis syndrome
Characterized by cryptorchidism , hypospadias, and poor sperm quality
Associated with pesticides and nonsteroidal estrogens
Klinefeltes syndrome
50x greater risk of mediastinal germ cell tumros, even though they don’t develop testicular tumros
Genetic risk factors for testicular germ cell tumors
KIT, BAK (receptor tyrosinase kinase)
Nonseminomatous tumors
Composed of cells that look like primordial germ cells or early gonadocytes
Nonseminomatous tumors
Composed of undifferentiated cells that look like embryonic stem cells and cells that have differentiated along different lineages
-creates yolk sac tumors, choriocarcinomas, and teratomas
60% of germ cell tumors are
Both aspects of seminomatous and nonseminomatous tumours
Pathogenesis germ cell tumor
Mostly come from precursor lesionLintratubular germ cell neoplasia (ITGCN)
-except for:yolk sac tumor, teratomas, adult spermatocytic seminoma
ITGCN occurs in utero, dormant until puberty
ITGCN consists of atypical primordial germ cells with large nuclei and clear cytpplasm. Also retain totipotential transcription factors (OCT34, NANOG)
ITGCN commonly has a duplication of the short arm 12 which is always found in all invasive germ cell tumors, and most patients with the lesion will progress to that level
-reduplication of the short arm of chromosome 12 (12p) in the form of an isochromosome i(12p), a cytogenetic alteration that is invariably found in invasive germ cell tumors regardless of histological type
Seminoma
Most comon type of germ cell tumor 50%
Who gets seminoma
20-30 year old, almost never infants
Seminoma has an identical tumor in the ovary called ____
Dysgerminoma
Getentics seminoma
Expresses isochromosome 12p and OCT3/4 NANOG
25% have gain of function KIT
Morphology seminoma
Large, round/polyhedral with a distinct cell membrane
Homogenous, lobulated, gray white masses, devoid of hemorrhage or necrosis
Tunica albuginea remains intact, but there can be extension to the epididymis, spermatic cord or scrotal sac occurs
Fibrous stroma produces irregular lobules with lymphocytic infiltrate
Clear or watery cytoplasm
Large central nucleus with 1-2 prominent nucleoli
Along with the other testicular germ cell tumors genetic factors, also express placental alkaline phosphatase (PLAP)
Some seminomas contain syncytiotrophoblasts and the patient willl have higher level of HCG but not as high as choriocarcinoma
Ill defined granulomas
Spermatic seminoma
Rare and slow growing testicular germ cell tumor
In patients over 65
Prognosis spermatic seminoma
Excellent
Indolent, doesn’t metasticize
Morphology spermatic seminoma
Soft, gray cut surface with mucosa cysts Mixture of cell types -medium sized cells with round nucleus and eosinophilia cytoplasm (most numerous) that may also have chromatin in the meiosis phase (spireme chromatin) -secondary spermatocytes -scattered giant cells
Lack lymphocytes, granulomas, syncytiotrophoblasts, extra-testicular sites of origin, and admixture with other germ cell tumors
NO ASSOCIATION WITH ITGCN
Embryonal carcinoma
In 20-30 year olds and more aggressive than seminomas
Morphology embryonal carcinoma
Poorly demarcated, small gray white mass with hemorrhage and/or necrosisi
Commonly extend through tunica albuginea into epididymis or cord
Grow in alveolar or tubular patterns, sometimes with papillary convolutions, but the undifferentiated lesions display sheets of cells
Cells are anaplastic, large with an epithelial appearance and indistinct border
Giant cells and mitotic figures
Genetics embryonal carcinoam
+ for OCT3/4, PLAP, CD30, cytokeratin
- for cKIT
Yolk sac tumor (endodermal sinus tumor
Most common testicular tumor in children <3
Prognosis yolk sac tumor
Good
Morphology yolk sac tumor
Infiltrating, homogenous, yellow white mucinous tumor
Cuboidal or flat neoplasticcells in a lacelike network
Schiller-duval bodies (primitive glomeruli) are found in 50%
-resemble endodermal sinuses
-consist of a mesodermal core with a central capillary and a visceral and parietal layer of cells
Eosinophilic hyaline globules with AFP a1-antitrypsin
-presence is AFP in the tumor cells is highly characteristic
Choriocarcinoma
Highly malignant neoplasm (<1% of all germ cell tumors)
Small palpable nodule, without testicular enlargement
What two types of cells are in choriocarcinoma
Cytotrophoblasts
Syncytiotrophoblasts
Cytotrophoblasts
Polygonal, distinct border+clear cytoplasm
Grow in cords or masses and have a single, fairly uniform nucleus
Syncytiotrophoblasts
Large, multinucleated cells
Abundant eosinophilic vacuolated cytoplasm with hCG-shoriocarcinomas pump out hCG
-hCG reaches very high levels in the serum
Teratomas
Occur at any age
Pure forms common in infants and kids (benign)
Pure forms of teratomas rare in adults (malignant)
In children, differentiated mature teratomas are __ and post pubertal teratomas are ___
Benign
Malignant
Teratomas are mixed with other germ cell tumors __% of the time
45
Teratoma: differentiation also endodermal, mesodermal and ectodermal lines
All three germ layers!
Teratoma morphology
Large, heterogenous appearance, hemorrhage and necrosis suggest admixture with embryonal andchoriocarcinoma
Haphazard differentiated mesoderm, ectoderm and endoderm neural , muscle cartilage, squamous , epithelial, thyroid gland, bronchial epithelial intestinal wall-all three layers
-all embedded in a fibrous or myxoid stroma
Mature or immature tissue
Do not have biomarkers
Teratoma with malignant transformation
Non germ cell malignancy developing within a teratoma
Non germ cell spreads outside the testis, it does not respond to chemo
Cure is dependent on ability to respect
Non germ cell malignancies retain isochromosome 12p, proving a colonial relationship to the preceding teratoma
Clinical features of testicular germ cell tumors
Painless enlargement of testis
Tumor spillage is possible during biopsy, so assume it is malignant and start with a radical orchiectomy
Retroperitoneal, paraaortic lymph nodes first involved as testicular tumors have a common lymphatic spread
Hematogenous spread to lungs (most common), liver, brain, bones
Seminoma clinical features
Remain localized to testis for long time
Radiosensitive
70% stage 1
95% with stage 1 or 3
Lymph nodes typically involved
Hematogenous spread later in disease
Best prognosis with 95% stage 1
Nonseminomatous germ cell tumor
More aggressive
Radioresistant
Metastasize early
Hematogenous spread more frequently
60% of patients present with advanced disease
90% acheived remission with chemo, except for pure choriocarcinoma has a worse prognossi
Histologically subtype does not influence prognosis significantly, thus all are considered as a group
Pure choriocarcinoma
Most aggressive NSGCT
No testicular enlargement
Rapid hematogenous spread
Lungs and liver are involved early in virtually every case
Testicular tumor stages
Stage I-confined to testis, epididymis, or spermatic cord
Stage II-distant spread confined to retroperitoneal nodes below the diaphragm
-persistent elevation of hCG or AFP concentrations following orchiectomy, even if the lymph appear normal, indicates stage II
Stage III-metastases outside the retroperitoneal nodes or above the diaphragm
Biomarkers yolk sac tumor
AFP
Biomarkers choriocarcinoma
HCG in 15%
NSGT biomarkers
AFP or hCG elevated at time of diagnosis (80%)
Seminomas biomarkers
HCG in 15%
Lactate dehydrogenase biomarker
Elevation correlates with the mass of the tumor cell
Allows assessment of the tumor burden
Serum biomarkers
Elevate testicular mass
Stage testicular germ cell tumors
Assess tumor burden
Monitor response to therapy
-with serial measurements, it is often possible to predict recurrence before the patient becomes symptomatic or develop any other lingual signs of relapse
Tumors of sex cord gonadal stroma
Leydig tumros
Sertoli cell tumors
Germ cell tumors -95%
Leydig cell tumors
2%
Most benign
10% invade/metasticize
Who gets leydig cell tumors
20-60 yo
What do leydig cell tumors produce
Androgens, estrogens, and/corticosteroids
Presetnation leydig tumors
Testicular swelling or changes resulting from hormone elaboration (gynecomastia), these are typically first seen in kids
Leydig cell tumor morphology
Grossly circumscribed nodules with a homogenous, golden brown cut surface
25% have eosinophilic reinke crystalloids (rod sharp)
Polygonal cells with abundant granular, eosinophilic cytoplasm and indistinct cell borders
Lipid droplets, vacuoles, lipofuscin pigment
Sertoli cell tumor
Hormonal silent and present as a testicular mass
Firm and small
10% malignant
Homogenous gray white to yellow masses of variable size lesions: tall, Coleman cells in trabecular
May form cords or tubules
Gonadoblastoma
Rare neoplasm comprised of a mixture of germ cells and gonadal stromal elements
Arise in gonads with testicular tubules
Germ cell component can become malignant giving rise to seminoma
Testicular lymphoma
Most common form of testicular tumor in patients older than 60
5% of all testicular neoplasms
Usually diffuse, large B cell non Hodgkin lymphomas
Disseminate widely
High incidence of CNS involvement
Othe testicular lymphomas
Burkitt
EBV+ extranodal NK/T cell lymphoma
Tunica vaginalis=
mesothelioma lined surface exterior to the testis
Hydrocele
Accumulation of serous fluid within the mesothelioma lined tunica vaginalis
-leads to enlargement of the scrotal sac that contains a clear fluid
Lined by mesothelioma cells
Hepatocellular
Accumulation of blood secondary to trauma, torsion, or generalized bleeding diathesis
Chylocele
Accumulation of lymphatic fluid secondary to lymphatic obstruction
-elephantiasis
Spermatocele
Local cystic accumulation of semen in dilated efferent ducts or ducts of the rete testis
Cariococele
Dilated vein in the spermatic cord
May be asymptomatic
Can contribute to infertility
Correct with surgery
Describe the prostate
Weight 20 grams and is divided into 4 zones Peripheral Central Transitional Peri-urethral
Which sone of the prostate do carcinomas most commonly aris
Peripheral
Which zone of the prostate does hyperplasia occur
Transitional
Tubular glands separated by ___ ___ devoid of a distinct capsule
Fibromuscular stroma
Glands are lined by two layers of epithelial cells
Basal layer of low cuboidal epithelium
Layer of columnar secretory cells
Normal growth of the prostate is controlled by what
Dihydrotestosterone DHT
DHT
Made by leydig cells and an enzyme called 2 5a reductase (T->DHT)
Castration
Widespread apoptosis _>prostatic atrophy
DHT stimulates _ cells
Stromal
Acute bacterial prostatis
Caused by similar pathogens as those that cause UTI-e coli, other gram negative rods, enterococci and staphylococci
Spread by intra-prostatic reflux of urine from the posterior urethra or from the urinary bladder
Sometimes spread via the lymph/blood from distant locations (lymphohematogenously)
Symptoms acute bacterial prostatis
Dysuria, fever, chills, perianal pain; prostate is tender and soft
Acute bacterial prostatis morphology
Minute, dissemination’s abscesses or large coalescent focal areas of necrosis or diffuse edema, congestiona and boggy suppurations of the entire gland
Biopsy acute bacterial prostatis
Contraindicated may lead to sepsis
Chronic bacterial prostatis
Frequent bouts of UTI lead to frequent prostatic infection
Symptoms chronic bacterial prostatis
Dysuria, pelvic discomfort and lower back pain
-can also be asymptomatic
Often no antecedent acute attack, and the disease appears insidiously and without obvious provocation
Infiltrates of plasma cells, lymphocytes, and macrophages
Antibiotics and chronic bacterial prostatis
Most antibiotics penetrate the prostate poorly—> bacteria find safe haven in the parenchyma and constantly seed the urinary tract
-history of recurrent UTI
Diagnose chronic bacterial prostatis
Based on leukocytosis int he expressed prostatic secretions with positive bacterial cultures
Nonbacterial prostatis
Most common prostatis
Symptoms nonbacterial chronic prostatis
Signs and symptoms just like that of chronic bacterial prostatis—dysuria, pelvic discomfort and lower back pain
Expressed prostatic secretions do show more than 10 leukocytes per high powered field but cultures are uniformly negative (likely to be an atypical bug (mycoplasma/chlamydia)
No history of recurrent UTI
Granulomatous prostatis
Specific-etiologic infectious agent identified
Non specific -etiologic infections agent cannot be identified
Diagnose granulomatous prostatis
Histologically which may be necrotizing or non necrotizing
-may mimic prostatic carcinoma clinically, grossly and histologically
The most common caus ein the US for granulomatous prostatis
Installation of BCG into the bladder for treatment of superficial bladder cancer
-this is of no clinical significance and doesn’t need treatment
Final granulomatous
Only in immunocompromised
Benign prostatic hyperplasia =nodular hyperplasia
Most common prostatic disorder defined as enlargement of prostate due to hyperplasia of prostatic stromal and epithelial cells
Often leads to urinary obstrucion -> bilateral hydronephrosis?
Characterization BHP
Large, fairly discrete nodules int he peri retinal region of the prostate
Stromal proliferation!!!
Incidence of BHP
20% of men by age 40 and 90% by 8-
No correlation between histology and clinical symptoms
Pathogenesis BHP
Increased # of epithelial cells and stromal components in the peri urethral area of the prostate
-no clear evidence of increased epithelial cell proliferation
Believed that hyperplasia stems from impaired cell death-still not a premalignant lesion
- assimilation os senescent cells in the prostate
- androgens increase cellular proliferation and inhibit cell death
T->DHT via 2 5a reductase
- type 2 5a-reductase found almost exclusively in prostate and stromal cells
- type 1 5a reductase converts T->DHT in the liter and skin; DNT from here may have endocrine effects
DHT activated FGF and TGF-b
-FGF mitogen for fibroblasts and other mesenchymal cells
TGF-b -inhibitor of epithelial proliferatgen
DHT induced growth factors act by increasing the proliferation of stromal cells and decreasing the death of epithelial cells
- with age, testosterone decreases, estrogen increases, and DHT status same
- estrogens increase sensitivity for DHT receptors in prostate
- testosterone really doesn’t play any role
- DHT (from leydig cells) has an increased selectivity on epithelial nuclear androgen receptors that induce glandular and stromal proliferation
Morphology BHP
Enlargement begins in the transitional zone and early nodules are made of stromal cells
After a there are epithelial cell nodules that arise
-causes compressiona nd obstruction or urethra->bilateral hydronephrosis?
BHP median lobe hypertrophy
Nodular enlargement that projects up into the floor of the urethra as a hemispheric mass directly beneath the mucosa
Gross morph BHP
Mostly glandular; yellow-pink, soft, and exude a milky white prostatic fluid
Mostly fibromuscular: large firm pale grey, do not exude fluid and are less clearly demarcated
Histology BHP
Glandular hyperplasia (with a double layer of epithelial cells: inner secretory columnar and outer low cuboidal) -occasionally, foci of reactive squamous metaplasia mimicking urothelial carcinoma are seen adjacent to prostatic infarcts in prostatis with prominent BPH
Diagnose BHP
Can’t be made with needle biopsy
Biopsies are too small to appreciate the modularity of the process and do not SJSU ally sample the transitional zone
Who gets BPH
Men 50s 90% have at 80
Black>white
Prestnation BHP
Nocturnal, urgency, hesitancy, difficulty in starting and stopping stream, overflow dribbling, dysuria, and have an increased risk of bacterial infections of the bladder and kidney
Can’t completely void bladder->reservoir of residual urine==commmon source of infection
Digital rectal exam BPH
Palpate a firm rubbery mass
Complete obstruction from BPH causes what
Urinary retention predisposing for bladder hypertrophy, systitis, and hydroureter/hydronephrosis
-sudden acute urinary retention needs catheterization as treatment
BPH premalignante
No
Treat BPH if mild
Decreasefluid intake, espicially before bed; decrease alcohol and caffeine intake
Treat more progressed BPH
Alpha blockers block smooth muscle tone int he prostate, 5 a-reductase (converts testosterone into HT) inhibitor or surgery (TURP_
TURP
Transurethral resection fo the prostate
Gold standard
First line if recurrent urinary retention
Adenocarcinoma of the prostate
Most common cancer in men (16% lifetime risk)
Tied with colorectal cancer for cancer related death
Uncommon in Asian
Common in blacks
Genetic risk for adenocarcinoma of prostate
Epigenetic alteration is hypermethylation (down regulation) of glutathione s transferase (GSTP1) gene on chronometer 11
GSTP1
Important part of the pathway that prevents damage from a wide range of carcinogens
First degree relative with adenocarcinoma of prostate
2x risk
Two first degree relatives with adenocarcinoma of prostate
5x risk
Mutation in BRCA2 adenocarcinoma of prostate
20x risk
HOXB1 mutation and adenocarcinoma
Greater risk
Rearrangement of ETS family transcription factor (ERG or ETV1) next to the androgen regulated TMPRSS2 promoter
Happens in 50% of white prostatic cancer patients
Makes the cancer more invasive, although it does not give a worse prognosis
Genomic deletions and amplification are more common in prostate cancer than point mutations involving oncogenes
In contrast to breast and colon cancers
Amplification of 8q24 (MYC oncogene)
Deletions involving PTEN tumor suppressor locus
Late stages include a loss of TP53
Deletions involving RB
Amplifications of the androgen receptor gene locus
Long trinucleotide expansion of CAGs in x linked androgen receptor gene causes a rare neurodegenerative disorder called ___ disease characterized by muscle cramping and fatigue
Kennedy
In Kennedy there is an __ relationship between the length of the expansion to androgen sensitivity
Inverse
Short expansion more sensitivity
Short expansion in ___, intermediate expansion in___ and long expansion in ____. Parallels the incidence and mortality of restate cancer in these groups
Black
Caucasian
Asian
Length of the repeat is __ related to rate at which prostate cancer develops in mice
Inverse
Possible precursor lesion
Begins with prostatic intraepithelial neoplasia (PIN)
Begins in the peripheral zone
PIN is not CIS
Environmental factors
Red meat, lycopenes(tomato), soy, VD
Set at early age and multipl partners, STD
Mechanical manipulation(vasectomy)
Diets high in fat which may inhibit VA absorption
Urban dwelling have increased risk of contraction and death due to potential exposure
Cadmium is a metal associated with carcinoma of prostate
North south gradient : Northern European more (VD sunlight thing)
SMOKING NOT LINKED
Clinical pancreatic adenocarcinoma
Obstruction of the urinary tract presenting like BPH
-most prostatic cancer arise peripherally away from the urethra and therefore urinary symptoms cure late
Rectal exam adenocarcinoma prostate
Firm, discrete nodules on rectal exam
- DRE and transreectal ultrasonography=low sensitivity and low specificity
- transrectal needle biopsy is needed to confirm the diagnosis
Metastatic disease adenocarcinoma of prostate
Finding of osteoblasts metastases by skeletal surveys or the much more sensitive radionuclide bone scanning is virtually diagnostic of prostate cancer in men: bony metastases are typically osteoblastic and this feature in men points strongly to prostatic origin
Paraneoplastic syndrome with adenocarcinoma prostate
DVT, DIC, nonbacterial thrombotic endocarditis
PSA and PAP levels are elevated in both adenocarcinoma and BPH
Elevated blood levels of PSA occur in associated with localized as well as advanced cancer
PAS and PAP are used as screens
-PSA lacks sensitivity and specificity
PSA is organ specific, not cancer specific
PCA3
Noncoding RNA overexpressed in 95% of prostate cancers
Currently used as an additional biomarker in patients suspected to have prostate cancer bc of elevated PSA but who had a negative prostate biopsy
Screen for prostate cancer
Begin at 50, blacks 40
Prognosis prostate cancer
Doubling time is slow (204 years) meaning it may remain asymptomatic for a long time, with an excellent 10 year survival rate
Treatment prostate cancer
90% 15 year survival
Surgery
Radiotherapy
Therapeutic effect of castration or treatment with anti-DHT->induced disease regression
- most tumors will eventually become resistant to androgen blockade
- loss of PTEN gene causes the tumor to no longer need androgens
Precursor to malignancy
Prostatic intraepithelial neoplasia
Morphology prostate cancer
Arises in the peripheral zone of the gland in 70% of cases, classically in a posterior location
May be difficult to see on gross, but palpable on rectal exam as it is typically found in the posterior region
Neoplastic tissue is gritty and firm
Local extension of prostate cancer
Commonly involves the pero prostatic tissue, seminal vesicles, and the base of the urinary bladder
Metastases spread via lymph to the obturator nodes and eventually to the para aortic nodes
Metastases spread via the blood mainly to the axial bones but also the the viscera in some cases
Describe the lesion of prostatic adenocarcinoma
Glands are typically smaller, more crowded and ess branched than the benign ones
Lined by a single layer of cuboidal or low columnar epithelium
The outer basal cell layer is absent
Benign prostate-contains basal cells
Malignant prostate-absent basal cells
Cytoplasm ranges from pale clear to amphilic
Large nuclei with one or more large nucleoli
Mitotic figures NO
Histology pancreatic adenocarcinoma
Prominent nucleoli, blue mucin, and perineural invasion
——-specific for prostate cancer
The tumor looks just like PIN, but the PIN are surrounded by a patchy layer of basal cells and an intact BM
Biomarkers prostatic adenocarcinoma
Alpha methylacyl-coenzyme a race made (AMACR)==upregulated in prostate cancer
Grading staging prostatic adenocarcinoma
Grading based on Gleason grading system which is determined by cellular architecture
Staging is determined based on invasion and metastasis
Gleason 1
Well differentiated , orderly packed, round, well circumscribed
Gleason 5
No glandular differentiation with tumor cells infiltrating the stroma in the form of cords, sheets, and nests
Multiple samples are taken where the dominant pattern (primary grade0 is added to the second most frequent artery (secondary grade) to get the Gleason score
If there is only one pattern, then primary grade==secondary grade and the score is doubles
If there are 3 patterns, the most common and highest scores are added together
Scores 206
Excellent prognosis
2 minimum gealson score and most well differentiated
3+4=7
Moderately differentiated tumors
3+4=7
Moderately to poorly differentiated tumros
8-10
Poorly differentiated tumros
10 Hughes and least differentiated
2-4
Small tumors found incidentally in TURP when looking for BPH
6-7
Majority of the treatable tumors found
8-10
Less likely to be cured
There staging
TNM designation
T1
Found incidentally either on TURP or needle biopsy
T1a do not progress when followed for 10 or more years
T1b are more ominous and have 20% mortality if left untreated
T2
Organ confined cancer
T2a and T3b
Tumors show extra prostatic extension, with and without seminal invasion
T4
Direct invasion of contiguous organs
Any spread of tumor to the lymph nodes regardless of extend is eventually associated with a fatal outcome
NO and N1==reflects presence or absence
Colloid carcinoma of prostate
Prostate cancer that reveal abundant mucinous secretions
Associated with thrombotic complications
Small cell cancer
Most aggressive variant of prostate cancer
Also know as neuroendocrine carcinoma
Almost all cases are rapidly fatal
Most common tumor secondarily involve the prostate
Urothelial cancer
Large invasive urothelial cancers can directly invade from the bladder into the prostate or
Carcinoma in site of the bladder can extend into the prostatic urethra and down into the prostatic ducts and acini
Morphology and clinical features of chronic complications of diabetes
Important morphological changes are related to the many late systemic complciations of diabetes
Morphology capillary basement membrane thickening diabetes
Widespread thickening of the GBM occurs in virtually all diabetic nephropathy
Diabetic nephropathy
Renal failure is second to MI in death
- Glomerular lesions
- Renal vascular lesions, principally arteriosclerosis
- Pyelonephritis, including necrotizing papillomas
Pure capillary BM thickening can only be detected with __
EM
When do diabetics get thickening of BM
As early as 2 years after diagnosis and 5 years 30% increase
Thickening is progressive with mesangial widening. Simultaneously there is thickening of the tubular basement membranes
Diffuse mesangial sclerosis chronic diabetes
Lesion consists of diffuse increase in mesangial matrix. There can be mild proliferation of mesangial cells early in the disease process but cell proliferation is not a prominent part of injury. The mesangial increase in typically associated with the overall B< thickening. The matrix depositions are PAs positive. As the disease progresses, the expansion of mesangial areas can extend to nodular configurations. The progressive expansion of the mesangium has been shown to correlate well with measures of deteriorating renal function such as increasing proteinuria
Nodular glomerulosclerosis
This is also known as intercapillary glomerulosclerosis or Kimmelstiel-Wilson disease . The glomerular lesions take the form of ovoid or spherical, often laminated, nodules of matrix situated in the periphery of the glomerulus. The nodules are PAS-positive. They lie within the mesangial core of the glomerular lobules and can be surrounded by patent peripheral capillary loops ( Fig. 24-39 ) or loops that are markedly dilated. The nodules often show features of mesangiolysis with fraying of the mesangial/capillary lumen interface and disruption of sites at which the capillaries are anchored into the mesangial stalks. The latter may produce capillary microaneurysms as the untethered capillaries distend outward due to force imparted by intracapillary blood pressure and flow. Usually, not all the lobules in individual glomeruli are involved by nodular lesions, but even uninvolved lobules and glomeruli show striking diffuse mesangial sclerosis. As the disease advances, the individual nodules enlarge and may eventually compress and engulf capillaries, obliterating the glomerular tuft. These nodular lesions are frequently accompanied by prominent accumulations of hyaline material in capillary loops (“ fibrin caps ”) or adherent to Bowman capsules (“ capsular drops ”). Both afferent and efferent glomerular hilar arterioles show hyalinosis. As a consequence of the glomerular and arteriolar lesions, the kidney suffers from ischemia, develops tubular atrophy and interstitial fibrosis, and usually undergoes overall contraction in size ( Fig. 24-40 ). Approximately 15% to 30% of individuals with long-term diabetes develop nodular glomerulosclerosis, and in most instances it is associated with renal failure
Renal atherosclerosis and arteriosclerosis
constitute part of the macrovascular disease in diabetics. The kidney is one of the most frequently and severely affected organs; however, the changes in the arteries and arterioles are similar to those found in other tissues. Hyaline arteriolosclerosis affects not only the afferent but also the efferent arteriole. Such efferent arteriolosclerosis is rarely, if ever, encountered in individuals who do not have diabetes
Pyelonephritis
Pyelonephritis is an acute or chronic inflammation of the kidneys that usually begins in the interstitial tissue and then spreads to affect the tubules. Both the acute and chronic forms of this disease are more common in diabetics than in the general population, and, once affected, diabetics tend to have more severe involvement. One special pattern of acute pyelonephritis, necrotizing papillitis (or papillary necrosis), is much more prevalent in diabetics than in nondiabetics
What are long term complications of diabetes
Retinopathy cataracts glaucoma
Microangiopathy, cerebral vascular infarcts, hemorrhage
HTN
Atherosclerosis
MI
Nephrosclerosis-glomerulosclerosis, arteriosclerosis, pyelonephritis
Islet cell loss-insulitis (type I) amyloid type II
Peripheral vascular atherosclerosis-gangrene and infections
Peripheral neuropathy
-autonomic neuropathy
What kills people with iabetes
Long term effects ,more than cute metabolic complications
Usually these happen 15-20 years after onset
Most common mortality of diabetics
Microvascular complications such as MI, renal vascular insuffiency, and cerebrovascular accidents
Diabetic nephropathy is a leading cause of end stage renal disease in the US
30-40% get(more type I)
Genes-higher in native americans, Hispanics, and blacks than whites
Early sign is albumin in urine, microalbuminuria
Microalbumina and diabetes is also sign of what
Increased CVD morbidity should do a macrovascular test
Without intervention microabulminiar turns to what
Macroalbuminuria usually with HTN
To end stage renal disease
20% type 2 75% type I by 20 years
Wilma tumor
Most common primary renal tumor of childhood and 4th most common pediatric malignancy in US
When do people get wilms
2-5
5-10% of wilms tumors involve both kidney and present about 10 months earlier, most likely due to what
Germline mutation
-first hit
Only 10% of non syndromes wilms tumors have ___ mutations suggesting that.a majority of these tumros are caused by other gene mutation
WT1
Nephrogenic rests
Putative precursor lesions of wilms tumors and are seen in the renal parenchyma adjacent to approximately 25-40% of unilateral tumros, nearly 100% of bilateral tumors
Share genetic alterations with the adjacent wilms tumors-preneoplastic
Important to document the presence of nephrogenic rests in the resected specimen bc these patients are at an increased risk of developing wilms tumor in the contralateral kidney and require frequent and regular surveillance for many years
WAGR
Wilms tumors
Aniridia
Genital anomalies
Metal retardation
Why get WAGR
Germline encoded deletions of 11p13 and the associated genes WT1 and PAX6-first hit
WT1 deletions is more at risk for wilms
-normal WT1->no increased risk of wilms
PAX6 mutation is more at risk for aniridia
- if only PAX6 is deleted->sporadic aniridia without wilms
- provides instructions for making a protein that is involved int he early development of the eyes, brain spinal cord and pancreas
Deny crash syndrome
Wilms 90%, gonadal dysgenesis (male psedohermpahroditism), and earl yonset nephropathy leading to renal failure
- characteristic glomerular lesion-diffuse mesangial sclerosis
- wilms tumor arising demonstrates bi allelic inactivation of WT1
Deny crash WT! Mutation
Dominant negative missense mutation in the zinc finger of the WT1 protein that affects DNA binding
-duffieicnt only in causing genitourinary abnormalities, not tumors
WT! Encodes a DNA binding TF that is expresssed within several tissues including the kidneys an dgonads
Critical for the normal development of the kidneys and gonads during embryogenesis
Individuals with mutation WT1 have increased risk of developing germ cell tumors called gonadoblastoma
Beckwith wiedemann syndrome
Organometallic, wilms(5%), macroglossia, hemihypertrophy, omphalocele, and abnormal large cellsin the Adriano cortex (adrenal cytomegaly)
Genes beckwith wiedemann
Chromosomal region involved 11p15.5 WT2
Normally expressed from one of the parent alleles with imprinting not he other copy
BWS has served as the model for a non classical mechanism of tumorigenesis-imprinting
Genetic basis of BWS is considerably more heterogenous in that no single gene is involved in all cases
IGF2 beckwith
Located in this region too and is typically only expressed by the paternal allele—maternal allele is imprinted
In some wilms tumors, there is less of imprinting-expression of both alleles
Or there is deletion of the maternal copy->uniparental disomy
Has greatest effect of tumorigenesis of all the WT@
CDKN1C beckwith
P57 mutation but have a lower risk of developing wilms
Have increased risk of hepatoblastoma, pancreatoblastoma, adrenocortical tumors, and rhabdomyosarcoma
Beta catenin beckwith
Some have beta catenin gain of function
Wilms tumor morphology
Large, solitary well circumscribed
10% bilateral or multi centric
Soft homogenous tan grey
Can have necrosis, cysts formation or hemorrhages
5% anaplasia=TP53 mutation
Can have heterozygous elements
Triphasic combination wilms
Blastemal-blue Small cells in sheets with few distinct features
Stromal-usually fibrotic or. Myxoid in nature
Epithelial-abortive tubules or glomeruli
Clinical features wilms
Present with large abdominal mass that may extend across midline or into pelvis
Hematuria, pain, bowel obstruction, HTN
Some present with pulmonary metastasis
Most can be cured
Anaplasia associated with worse prognosis (need to sample tumor well)
Loss of genetic material 11q and 16q, or gain of 1q worse prognosis
Increased risk of seconda primary tumors of bone, soft tissue sarcomas, leukemia, lymphoma, and breast cancer to the germline mutation or therapy
