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Cyberfriends: The help you're looking for is probably here.
Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.
DoctorGeorge.com is a larger, full-time service.
There is also a fee site
at www.afraidtoask.com.
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With one of four large boxes of "Pathguy" replies. |
I'm still doing my best to answer
everybody.
Sometimes I get backlogged,
sometimes my E-mail crashes, and sometimes my
literature search software crashes. If you've not heard
from me in a week, post me again. I send my most
challenging questions to the medical student pathology
interest group, minus the name, but with your E-mail
where you can receive a reply.
Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource.
KCUMB Pathology Club
Freely have you received, freely give. -- Matthew 10:8. My
site receives an enormous amount of traffic, and I'm
still handling dozens of requests for information weekly, all
as a public service.
Pathology's modern founder,
Rudolf
Virchow M.D., left a legacy
of realism and social conscience for the discipline. I am
a mainstream Christian, a man of science, and a proponent of
common sense and common kindness. I am an outspoken enemy
of all the make-believe and bunk that interfere with
peoples' health, reasonable freedom, and happiness. I
talk and write straight, and without apology.
Throughout these notes, I am speaking only
for myself, and not for any employer, organization,
or associate.
Special thanks to my friend and colleague,
Charles Wheeler M.D.,
pathologist and former Kansas City mayor. Thanks also
to the real Patch
Adams M.D., who wrote me encouragement when we were both
beginning our unusual medical careers.
If you're a private individual who's
enjoyed this site, and want to say, "Thank you, Ed!", then
what I'd like best is a contribution to the Episcopalian home for
abandoned, neglected, and abused kids in Nevada:
My home page
Especially if you're looking for
information on a disease with a name
that you know, here are a couple of
great places for you to go right now
and use Medline, which will
allow you to find every relevant
current scientific publication.
You owe it to yourself to learn to
use this invaluable internet resource.
Not only will you find some information
immediately, but you'll have references
to journal articles that you can obtain
by interlibrary loan, plus the names of
the world's foremost experts and their
institutions.
Alternative (complementary) medicine has made real progress since my
generally-unfavorable 1983 review. If you are
interested in complementary medicine, then I would urge you
to visit my new
Alternative Medicine page.
If you are looking for something on complementary
medicine, please go first to
the American
Association of Naturopathic Physicians.
And for your enjoyment... here are some of my old pathology
exams
for medical school undergraduates.
I cannot examine every claim that my correspondents
share with me. Sometimes the independent thinkers
prove to be correct, and paradigms shift as a result.
You also know that extraordinary claims require
extraordinary evidence. When a discovery proves to
square with the observable world, scientists make
reputations by confirming it, and corporations
are soon making profits from it. When a
decades-old claim by a "persecuted genius"
finds no acceptance from mainstream science,
it probably failed some basic experimental tests designed
to eliminate self-deception. If you ask me about
something like this, I will simply invite you to
do some tests yourself, perhaps as a high-school
science project. Who knows? Perhaps
it'll be you who makes the next great discovery!
Our world is full of people who have found peace, fulfillment, and friendship
by suspending their own reasoning and
simply accepting a single authority that seems wise and good.
I've learned that they leave the movements when, and only when, they
discover they have been maliciously deceived.
In the meantime, nothing that I can say or do will
convince such people that I am a decent human being. I no longer
answer my crank mail.
This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.
This page was last updated November 12, 2009.
During the fourteen years my site has been online, it's proved to be
one of the most popular of all internet sites for undergraduate
physician and allied-health education. It is so well-known
that I'm not worried about borrowers.
I never refuse requests from colleagues for permission to
adapt or duplicate it for their own courses... and many do.
So, fellow-teachers,
help yourselves. Don't sell it for a profit, don't use it for a bad purpose,
and at some time in your course, mention me as author and KCUMB as my institution. Drop me a note about
your successes. And special
thanks to everyone who's helped and encouraged me, and especially the
people at KCUMB
for making it possible, and my teaching assistants over the years.
Whatever you're looking for on the web, I hope you find it,
here or elsewhere. Health and friendship!
OBJECTIVES: The student will give a reasonable account of the origins,
symptoms, signs, epidemiology,
and anatomic pathology of the common bladder lesions.
The student will recognize the common cystoscopic and biopsy
lesions. As men draw near the common goal,
Keep The Water Flowing.
QUIZBANK:
Lower urinary (all)
INTRODUCTION: Easy unit.
{15588} normal bladder, gross
You remember that normal transitional epithelium (better, "urothelium")
is designed to cover surfaces that change their
areas rapidly.
Bladder urothelium
should be six or fewer cells thick (really, strata of nuclei), less when the
bladder is full. The superficial layer exhibits the famous protective
layer of broad, flat "umbrella cells", while the basal layer is
famous for its ability to flatten out.
* Urothelium in the renal pelvis tends to have fewer
layers, usually 3-5. Urothelium usually produces a bit of mucin,
which explains those few bubbles in the toilet bowl.
Often tumors that arise from
urothelium produce mucin also. This does not make them
"adenocarcinomas".
Uroplakin III stains normal urothelium and many urothelial cancers, being quite specific.
When urothelium turns to urothelial papilloma-carcinoma, it tends to do so in
multiple places (Nowell's law
again, since urothelial cells seldom divide, they
are all the more readily overgrown by mutants with more
of a propensity to divide). Forty percent of tumors are multiple at presentation.
This has a lot to do with "frequent recurrences after surgery".
{14941} normal urothelium
A STRICTURE is fibrous tissue partially or totally occluding the lumen of a narrow hollow organ,
usually the ureter or urethra. They may be congenital, but is more often
post-injury scarring (gonorrhea, instrumentation,
stone).
URETER PROBLEMS
You know the anatomy. The muscle is interlaced, without real layers.
Acute obstruction causes renal colic, which is often excruciating. Chronic
obstruction is usually asymptomatic, though the kidney won't function and will eventually atrophy.
Places where stones, etc., hang up are (1) the pyelo-ureteric junction; (2) the pelvic brim; (3) the
ureterovesical junction.
DOUBLE URETER (bifid ureter) is whole or partial duplication, with two pelvises in the kidney. No big
deal. A few percent of folks have this minor variant.
{15711} bifid ureter, gross
Any obstruction to urinary flow (in the ureter or elsewhere) during fetal life will result in
CYSTIC DYSPLASIA of the portion of the kidney that isn't being properly drained.
An INCOMPETENT URETEROVESICAL VALVE is a common birth defect that causes reflux and predisposes
to kidney infections. It may stay open all the time, or open during micturition.
How to manage these children remains controversial.
Many of these children undergo surgical repair, but the benefit of
surgery over simply treating infection is not clear (Lancet 357:
1329. 2001).
When there is actual deformity
of the ureter, the kidney disease is a mix of renal dysplasia (which is part of the birth
defect) and actual damage from the bacterial infections.
* A variety of defects have been reported in valves that merely
reflux during micturition, including findings as simple as lack of smooth muscle
and as complicated as the lack of certain obscure electrical cells and their
gap junction protein (J. Urol. 174: 1981, 2005.)
HYDROURETER (i.e., dilated ureter) has several causes
CONGENITAL
PREGNANCY ("estrogen relaxes smooth muscle", etc.)
OBSTRUCTION
Ureter cancer
CHAGAS'S DISEASE
{18791} pyelonephrosis and pyoureters, gross
A very large ureter is called a MEGA(LO)URETER.
* "Follicular ureteritis" is an archaic name
for big lymph nodules. "Ureteritis cystica" and "Brunn's nests" match their
counterparts in the urinary bladder.
Almost all cancer of the ureter is "urothelial carcinoma", a better
term than the old name "transitional cell carcinoma". Like cancer of the renal pelvis, this is a
variation on bladder cancer, with the same risk factors and the same tendency to arise multifocally over
the urothelium.
{10580} urothelial carcinoma, ureter
NON-NEOPLASTIC DISEASE OF THE URINARY BLADDER
Anatomic and clinical pathology have not explained "overactive
bladder", a common problem especially in older women, with discomfort,
frequency, urgency, and/or urge incontinence.
EXSTROPHY of the urinary bladder results from failure of the pubis to form properly. This is a messy
problem for the surgeon to repair, and of course, infection and poor hygiene are terrible problems.
Update Urol Clin. N.A. 31: 417, 2004. Thankfully, today most of these
patients are spared kidney damage despite the risk of ascending infections (J. Urol. 168: 2579, 2002).
{10742} exstrophy of the urinary bladder
PERSISTENT URACHUS, if it is or becomes patent, results in urine dribbling out the navel. More often, urachal cysts
remain. When an adenocarcinoma arises deep in the front of the bladder
wall, it has probably arisen from urachal remnants.
CYSTOCELE is drooping of a portion of the urinary bladder downward into the more caudal areas of the
pelvis. This usually follows childbirth. This may remain filled with urine after voiding, or obstruct
the outlet, inviting infection in either case.
HYPERTROPHY OF THE BLADDER WALL results from obstruction, usually from prostatism. The muscle
bundles ("trabeculae") become much more visible ("trabeculation").
{24445} hypertrophy of the bladder from prostatism, gross
DIVERTICULA OF THE BLADDER may be congenital, but more often result from a portion of the mucosa
pooching out ("pulsion diverticulum") between two strands of hypertrophied muscle in a person
suffering from chronic obstruction. This may produce the famous "double urination" (* pis à deux,
they call it in France),
and/or a place for stasis, inviting infection, and/or a place
where bladder stones can form.
Purists: Obviously pulsion diverticula of the bladder are pseudodiverticula, just like in the colon.
If a cancer forms here, it has been
considered very serious, since there is no muscularis propria (detrusor)
to slow the invasion. New numbers with fairly good survival statistics (i.e.,
it's the malignant potential of the tumor rather than the presence or
absence of a barrier): Urol. 50: 697, 1997; J. Urol. 170: 1761, 2003.
BLADDER STONES usually result from infection, and are composed of magnesium ammonium
phosphate.
{21030} bladder stones
CYSTITIS is usually of bacterial origin, and has the same story as common pyelonephritis, which it
precedes. Urosepsis still kills many adults of both sexes.
The pathology is what you'd expect. Neutrophils abound in the acute
phase. In longstanding disease, there is a chronic inflammatory infiltrate
and there may be much fibrosis.
Vitamin C is occasionally still recommended by "natural healing"
types to prevent bladder infections.
It failed the most recent controlled study miserably (Spinal Cord 34: 592, 1996); eleven years later, there's been no more work on the subject.
* The uncommon "emphysematous cystitis" is an unfortunate term for infections with bugs that have
formed gas (South. Med. J. 91: 785, 1998). "Bullous cystitis"
is an archaic term for a bladder infection
with so much edema between the epithelium and the muscularis
propria that it looks like water balloons.
"Encrusted cystitis" is fairly common nowadays, and is
due to urea-splitters. It features
magnesium ammonium phosphate plastered over the bladder mucosa.
Almost all cases are caused by Corynebacterium urealyticum, and this is
becoming a bane of the renal transplant service (Eur. Uro. 39: 446, 2001).
* All about symptomatic urinary tract infections on young women, with the risk factors of recent
intercourse, use of diaphragm and spermicide, and past history of urinary tract infections: NEJM
335: 468, 1996 (still great).
During the 1980's, there was a push to antibiotic-treat all little girls with
asymptomatic bacteriuria, often for a long time. This never made much
sense to me and now it's not much discussed.
The folk wisdom that cranberry juice prevents and helps cure bladder infections is
clearly true (JAMA 271: 751, 1994, others). It prevents
E. coli from forming fimbriae (J. Urol. 159: 559, 1998),
so they cannot bind to their sanctuaries on the bladder mucosa.
It's
the proanthocyanidins (NEJM 339: 1085, 1998).
* POLYPOID CYSTITIS is not a tumor at all, but a reactive
overgrowth (collagen and/or extra ground substance) in response to
ongoing inflammation (usually an indwelling catheter). It may be bullous (i.e., look like blobs) or
papillary (i.e., look like weeds). Update Int. Urol. 34: 293, 2002.
CHEMOTHERAPY CYSTITIS results from cyclophosphamide ("Cytoxan") or busulfan ("Myleran")
administration, and RADIATION to the pelvic area can also produce a vicious cystitis.
* "Giant cell cystitis" should not be diagnosed.
It's an old term for the presence of
of giant urothelial cells in patients who have had radiation or chemotherapy.
HUNNER'S INTERSTITIAL CYSTITIS ("painful bladder syndrome") (Urology 49(5A):
14, 1997; Am. Fam. Phys. 64: 1199, 2001) is a poorly-understood process in which all three
layers of the
bladder become chronically inflamed.
Patients are mostly women, and they often have considerable
pain and urgency. The pain must be due, at least in part, to
excess permeability of the urothelium to the potassium in the urine
(Urology 57: 428, 2001; the same is apparently true of the equally-mysterious,
painful
"urethral syndrome".)
Probably the bladder epithelium becomes over-permeable, but morphologic
changes are not obvious and the altered molecular structure is only now
being worked out by pathologists (J. Urol. 171: 1554, 2004; Am. J. Clin. Path. 125: 105, 2006.)
Visible on cystoscopy are distinctive new-vessel formations ("glomerulations" cited above)
that are now considered important in establishing the diagnosis clinically.
No histopathologic lesion is diagnostic. However, pathologists
are now looking at several distinctive findings, each correlating
with severity, and each requiring special stains.
A different pattern of cytokeratins in the epithelium, without
any diffence in morphology (Am. J. Clin. Path. 125: 105, 2006).
VEGF and other stains showing the glomerulations (J. Urol. 172: 945, 2004),
and S100 to demonstrate
an often-striking increase in little nerve fibers in the mucosa
(J. Urol. 177: 142, 2007).
No special stains are required to show the mucosal edema, hemorrhage,
epithelial loss and/or granulation tissue in severe cases.
"Hunner's ulcer" is the advanced stage,
with mucosal breakdown.
MALAKOPLAKIA is a curious macrophage-rich response to proteus infections. The cells seem to have
some problem phagocytizing the bugs.
Grossly, you'll see soft ("malakos" in Greek) yellow plaques.
Microscopically, you'll see foamy, lipid-laden (* "von Hensemann's) macrophages with calcified
spherules ("Michaelis-Gutmann bodies"). Nobody knows much about this.
* The cure is to use an antibiotic that penetrates macrophages (Lancet 339: 148, 1992); quinolones
seem best (Arch. Int. Med. 156: 577, 1996).
{25276} malakoplakia, histology
BRUNN'S NESTS are little balls of urothelial-type cells in the lamina propria of the bladder.
They are very common and probably mean nothing. Look for them and you'll
probably find them in most bladders.
CYSTITIS
CYSTICA is like Brunn's nests, only with a hole in the middle.
This is supposedly a Brunn's nest that is responding to irritation.
In CYSTITIS GLANDULARIS, the cells of cystitis cystica produce mucin;
if there are goblet cells, the pathologist will note "with intestinal metaplasia".
These are all pathologists' curiosities rather than something to worry
about, but you need to know the names as they will often appear on biopsy reports.
{25279} Brunn's nests, histology
SQUAMOUS METAPLASIA in endemic areas
usually results from infestation with Schistosoma hematobium {09863} Schistosoma hematobium egg, bladder
{24020} urothelial dysplasia with squamous metaplasia; in the background
of urothelial neoplasia, squamous metaplasia
means little or nothing
Don't forget AMYLOID and AMYLOIDOMA as causes of hematuria (the brittle amyloid-laden vessels
crack.)
* STRESS INCONTINENCE ("I lose urine when I cough")
is a common problem, especially in women who have borne children. The problem
is usually in the structures that support the bladder outlet.
Surgery
often helps.
Rupture of the bladder from trauma is very serious.
To this day nobody knows
exactly why
Virginia Rappe's bladder ruptured. Having looked over the trial testimony,
it looks like an overcall to me, and that Mr. Arbuckle was guilty
only of hanging out with the wrong people But
Mr. Arbuckle's career was ruined.
The story does not show humankind at its finest.
I would urge you to read up on the case, when you get a chance.
It may cause you to reach the same decision that I have, i.e.,
that in cases involving allegations of weird (and even wildly improbable)
sexual abuse, everyone goes crazy and our criminal
justice system simply cannot distinguish guilt from innocence.
{25306} amyloidoma, gross
BLADDER TUMORS
UROTHELIAL CARCINOMA is the usual "bladder cancer" of older adults. It strikes around 40,000
men per year (4th most common cancer), and 14,000 women (9th most common cancer). Around
1/3 of cases eventually prove fatal.
{18788} urothelial carcinoma, gross
The new WHO/International
Society of Urologic Pathologists system is now standard, and this is what we'll
teach you.
Review J. Clin. Path. 61: 3, 2008.
The genetics of bladder cancer and its precursor lesions is now well
worked out (J. Urol. 171: 419, 2004; Arch. Path. Lab. Med. 130:
844, 2006). The "papillary pathway" (80%) and the "non-papillary pathway"
(from flat carcinoma-in-situ, 20%) are distinct.
The papilary lesions typically have mutant H-ras and overexpressed EGFR.
* Messenger RNA studies can be obtained easily from the cells of bladder washings.
The best urine in which to look for cancer cells
is the second-voided of the day (i.e., the cells have
not deteriorated in the bladder). A hefty dose of oral vitamin C after first void
(which goes out in the urine) helps preserve the cells.
For some reason, and unlike most other cancers,
the grade of a urothelial carcinoma is unlikely to
get worse over time; after therapy, it may even get better (i.e., we killed
off all the really anaplastic cells): J. Urol. 169: 2106, 2003.
Urothelial tumors are either flat
or papillary.
THE PAPILLARY LESIONS are most likely to present with hematuria,
either grossly or on microscopic urinalysis. Of course this results
from papillary fronds twisting off and bleeding slightly. Of course,
any mass lesion (papillary or otherwise) can obstruct.
As long as this is the only problem, it doesn't
mean much, other than
Nowell's law is probably operating, i.e.,
a mutation has allowed overgrowth.
UROTHELIAL DYSPLASIA ("low-grade intraurothelial lesion / intraurothelial
neoplasia") is diagnosed
when there
is some coarsening of the nuclear chromatin in the urothelium,
the nuclei have perhaps lost their usual orientation with long axis
perpendicular to the basement membrane,
and perhaps there's a mitosis or two, usually in the lower layers.
Or there may only be a few anaplastic cells among healthy-looking cells ("pagetoid canceriation").
Or the cells might just be big ("large cell non-pleomorphic").
Or the cells might look like oat cells ("small cell in situ").
Or only a few malignant cells might be stuck to the wall here and there ("clinging").
Or the cancer cells might grow only along the bottom, the the upper urothelium be nice
with good umbrella cells ("undermining cancerization").
* Future pathologists: A fooler is BK polyoma virus in the immunocompromised.
Another is chemotherapy effect after mitomycin C and/or thiotepa.
Let us worry about this.
Usually
asymptomatic, CIS may be uncomfortable if it allows backleak of electrolytes, since the
salty urine stimulates pain fibers in the submucosa. On cystoscopy, if it is visible
at all, it looks
smooth and red (i.e., the lamina propria is inflamed because
substances from urine leak through) or is sometimes detected only by sampling of the mucosa
by biopsy.
Carcinoma in situ is notoriously unpredictable, and much more
ominous than an actual mass lesion without invasion (J. Urol. 172: 882, 2004).
Around 20-50% of known cases of
carcinoma in situ turn into invasive cancer within five years
(Am. J. Clin. Onc. 21: 217, 1998),
and it can sometimes metastasize without an identifiable invasive mass.
We believe that many (most?) invasive
cancers start here rather than in papillary lesions;
the numbers are still being sorted out.
Papillary urothelial (papillary / exophytic urothelial tumors / lesions): UROTHELIAL PAPILLOMAS (grade 0 tumors) grow
up from the mucosa ("like a glove with fingers"),
have fibrovascular cores,
and are covered with normal
urothelium (i.e., no analasia, no more than 6-8 nuclear layers).
They are almost always incidental findings.
PAPILLARY UROTHELIAL HYPERPLASIA: Like flat urothelial hyperplasia,
with some papillary growth but not good fibrovascular cores.
PAPILLARY UROTHELIAL TUMOR OF LOW MALIGNANT POTENTIAL (* PUNLMP, the old "Grade I")
are
papillary lesions with good fibrovascular cores, and
in which the surface epithelium the cells
show minimal anaplasia and/or minimal architectural distortion and/or more than
7 layers without anaplasia. A few fused fronds perhaps, and if there
are mitotic figures they're still low in the epithelium. These tumors
seldom turn invasive but maybe a third recur.
LOW-GRADE PAPILLARY UROTHELIAL CARCINOMAS (* similar to the old "Grade II")
have papillary growth with good fibrovascular cores,
and urothelium similar to flat dysplasia.
This is a very common diagnosis.
Even the umbrella layer is often intact in
one of these "low-grade" tumors. Another helpful sign of cancer is loss of
the usual "clear cytoplasm" seen in some cells in a normal urothelium.
These little
cancers usually remain asymptomatic for years. About half will recur,
about 10% will eventually turn invasive, and a few percent of these patients
will die of bladder cancer.
HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMAS (* "Grade III")
are obviously anaplastic. There are fibrovascular cores,
but the urothelium looks like flat carcinoma-in-situ.
They have usually
invaded before they produce symptoms.
If discovered early (i.e., you screen everybody for hematuria every year),
though, only a minority invade (Br. J. Urol. 83:
957, 1999).
As you'd expect, bladder discomfort, painless hematuria, and infection are typical
presentations.
Regardless of grade, urothelial carcinomas are "superficial" until they extend among
the inmost fibers of the muscularis propria. (There is seldom an obvious a muscularis
mucosae in the bladder; if there is, invasion of this doesn't count against
the tumor being "superficial".)
Spotting superficial invasion:
Aggressive papillary lesions can be identified
by staining for p53, high division index (Ki-67), and
having cytokeratin 20-positivity throughout the epithelium rather
just in the surface (as in normal urothelium).
Great photos: Am. J. Clin. Path. 121: 679, 2004; Cancer 97:
1876, 2003.
The correlation with the new grading system is excellent.
Even the
precursor lesions of bladder cancer
typically have abnormal staining patterns.
In 1998 I predicted the success of the Lewis X antigen as a screening
tool for urine; it's proved the most sensitive though least specific of
a series of markers that now also include several other biotech-based
assays (World J. Urol. 22: 145, 2004).
Finding the malignant areas to biopsy using laser-induced
autofluorescence: J. Urol. 159: 1871, 1998.
Most recently, multiprobe fluorescence in-situ hybridization has been
introduced (J. Urol. 176: 44, 2006) and has proven
far more sensitive (70% vs 35%) than traditional cytology,
though cytology still picks up many lesions that fluorescence misses;
both have very few false-positives (Cancer Genet. Cytogenet. 173:
131, 2007). The prototype is "Urovision" FISH kit which looks for aneuploidy
in chromosomes 3, 7, 9p21, and 17 -- it also seems to work for the less common
histologic types (Am. J. Clin. Path. 130: 552, 2008).
Patients under surveillance for recurrence are also followed in this way (Am. J.
Clin. Path. 127: 295, 2007); no one really knows what to do
when there is a "molecular recurrence" but no visible recurrence, though
the majority will have a recurrence within two years.
Cathepsin L may come into use for surveillance in patients with previous neoplasia (J. Urol. 179: 478, 2008).
RISK FACTORS for urothelial carcinoma include
Lynch's nonpolyposis colon cancer
family syndrome (x14, J. Urol. 160: 466, 1998)
The urothelium, of course, is exposed to many carcinogens, which we
may think are concentrated in the urine; nobody should be surprised to learn
that the more water you drink, the lower your risk of bladder cancer
(NEJM 340: 1390, 1999).
Your lecturer, after reviewing the evidence, believes that allegations that
cyclamates and saccharin cause bladder cancer in humans are
rubbish, and the ban resulted from
junk science and politics-as-usual. These were given in preposterously large doses to experimental animals,
and nobody has been able to show the expected epidemiologic links (big reviews
for both NEJM 302: 537, 1980; JAMA 240: 349, 1978).
Even the JAMA, not noted downplaying risks to the public,
belatedly agreed the claims of a link between saccharin
and cancer were groundless (JAMA 254: 2622, 1985).
* Future pathologists: How to "gross in" a bladder: J. Urol. 171: 1823, 2004; Cancer 100:
2470, 2004; Arch. Path. Lab. Med. 127: 1263, 2003.
ADENOCARCINOMA of the bladder is uncommon. Two types are
distinguished primarily by location.
The other arises around the trigone
(usually) from "cystitis glandularis" (maybe) or "colonic metaplasia" (known to be
premalignant).
* Clear cell variant: Arch. Path. Lab. Med. 132: 1417, 2008.
SQUAMOUS CELL CARCINOMA of the bladder usually arises in squamous metaplastic
epithelium, i.e., the patient has schistosomiasis PHEOCHROMOCYTOMA: Urinating turns from a pleasure to a headache. Uncommon, but
memorable.
* Children are prone to exotic mesenchymal tumors, especially
RHABDOMYOSARCOMAS. To diagnose a rhabdo here, you'll want
to see plenty of anaplasia, a cambium layer,
and at least a few good round rhabdomyoblasts.
* Small-cell carcinoma of the bladder, which often arises
in a more conventional-style bladder cancer, looks like oat-cell carcinoma
of the lung on microscopy and electron microscopy, and is aggressive as you'd expect,
though cures aren't unknown (Cancer 103: 1172, 2005).
There is a large-cell neuroendocrine variant as well (Am. J. Clin. Path. 128: 733, 2007).
* The micropapillary variant of urothelial carcinoma looks like serous
cystadenocarcinoma of the ovary (Am. J. Surg. Path. 18: 1224, 1994. It seems to be best treated by surgery (Cancer 110: 62, 2007).
* The treacherous, newly-described NESTED VARIANT
looks like von Brunn's nests but with smaller cells. Despite a benign
appearance, it's thoroughly malignant and invasive (Arch. Path. Lab. Med. 131: 1725, 2007).
* NEPHROGENIC ADENOMA ("nephrogenic metaplasia") is a papillary mass of loose,
inflamed connective tissue
with hobnail cells all over its surface.
It's probably a curious reparative response rather than a true
tumor, since it usually follows injury.
Tubules resembling kidney collecting
ducts and Henle's loops penetrate deep into it. As you would expect, patients
present with bleeding. It is considered harmless. Update Adv. Anat. Path. 13:
247, 2006. URETHRA
In either sex: Patients complaining of urethritis symptoms need to be questioned about
consumption of jalepiño peppers.
POSTERIOR STRICTURE: A man's problem. Often congenital. The urologist can help you.
URETHRAL CARUNCLE: A woman's problem, often developing later in life, near the opening
of the urethra. Perhaps it begins with plugging of the ducts of the glands.
It is an uncomfortable
lesion with mixed inflammation of the lamina propria, and often with
pseudoepitheliomatous hyperplasia of the overlying squamous
epithelium.
{14937} ureter (cross section), normal
BIBLIOGRAPHY / FURTHER READING
I urge anyone interested in learning more about
this topic in pathology
to consult these standard textbooks.
In my notes, the most helpful current
journal references are embedded in the text.
Students using these during lecture strongly prefer this.
And because the site is constantly being updated,
numbered endnotes would be unmanageable.
What's available online, and for whom, is always changing.
Most public libraries will be happy to help you get an article
that you need. Good luck on your own searches, and again,
if there is any way in which I can help you, please contact me at
scalpel_blade@yahoo.com.
No texting or chat messages, please. Ordinary e-mails are welcome.
Health and friendship!
I am presently adding clickable links to
images in these notes. Let me know about good online
sources in addition to these:
MedEdPORTAL -- American Association of Medical Colleges. Primarily for medical school faculty.
Pathology Education Instructional Resource -- U. of Alabama; includes a digital library
Pathopic -- Swiss site; great resource for the truly hard-core
Syracuse -- pathology cases
Alabama's Interactive Pathology Lab
"Companion to Big Robbins" -- very little here yet
Alberta Tumor Photos -- and lots more. Highly recommended.
Biomedical
Image Archive
Chilean Image Bank -- General Pathology -- en Español
Chilean Image Bank -- Systemic Pathology -- en Español
Connecticut
Virtual Pathology Museum
Australian
Interactive Pathology Museum
Interactive Pathology Museum
Semmelweis U.,
Budapest -- enormous pathology photo collection
Iowa Skin
Pathology
Loyola
Dermatology
History of Medicine -- National Library of Medicine
KU
Pathology Home
Page -- friends of mine
The Medical Algorithms Project -- not so much pathology, but worth a visit
National Museum of Health & Medicine -- Armed Forces Institute of Pathology
Telmeds -- brilliant site by the medical students of Panama (Spanish language)
U of
Iowa Dermatology Images
U Wash
Cytogenetics Image Gallery
Urbana
Atlas of Pathology -- great site
Visible
Human Project at NLM
Karolinska Institutet -- pathology links
Johns Hopkins CPC's
U. of Virginia Case Studies
Oklahoma Teaching Cases
Indiana U. Teaching Cases
SUNY Histopathology
West Virginia Case of the Month
Upstate NY Cases -- works only on some browsers
Society for ultrastructural pathology -- electron microscope cases
WebPath:
Internet Pathology
Laboratory -- great siteEd Lulo's Pathology Gallery
Also:
Bryan Lee's Pathology Museum
Dino Laporte: Pathology Museum
Tom Demark: Pathology Museum
Dan Hammoudi's Site
![]()
Medmark Pathology -- massive listing of pathology sites
Estimating the Time of Death -- computer program right on a webpage
Pathology Field Guide -- recognizing anatomic lesions, no pictures
St.
Jude's Ranch for Children
I've spent time there and they are good. Write "Thanks
Ed" on your check.
PO Box 60100
Boulder City, NV 89006--0100
More of my notes
My medical students
Clinical
Queries -- PubMed from the National Institutes of Health.
Take your questions here first.
HealthWorld
Yahoo! Medline lists other sites that may work well for you
We comply with the
HONcode standard for trustworthy health
information:
verify
here.
Could anything be sadder
Than he who, master of his soul,
Is servant of his bladder?
-- Anonymous!
-- "The First Principle of Urology"
Kidney and Lower Urinary
Photo Library of Pathology
U. of Tokushima
Lower Urinary / Male
Taiwanese pathology site
Good place to go to practice
Urologic Path
Surgical Pathology Atlas
Nice photos, hard-core
Bladder Exhibit
Virtual Pathology Museum
University of Connecticut
Kidney & Urinary Tract
Brown Digital Pathology
Some nice cases
{15771} normal bladder, gross
{15772} normal bladder, gross
{15587} normal bladder and prostate, gross
{15114} normal bladder, histology
{15120} normal bladder, histology
{15326} normal bladder, histology
{25266} normal bladder histology
Normally,
it takes about a year to replace itself, so you're unlikely to see any mitotic figures until there's
serious disease.
{14937} normal ureter histology
{10022} normal urothelial, cytology
This is a very important cause of kidney failure in children.
* This has found recent support in studies of the familial
form of the illness: J. Urol. 176: 1842, 2006.
Bladder cancer
Prostate cancer
Cervix cancer
Metastases in the para-aortic lymph nodes
Etc.
You learned in physiology and neuroscience class about the various problems with voiding when the
cerebral cortex and bladder are separated. When the bladder is inflamed, urinating can be uncomfortable,
and often the bladder contracts with excessive force (urgency). See "Big Robbins" for a common-sense list of causes of bladder
outlet obstruction.
If it's not inflamed, it's probably
a fibroepithelial polyp instead (Am. J. Surg. Path. 29: 460, 2005),
a benign tumor of alarming appearance.
A really bloody-looking cystitis ("hemorrhagic cystitis") should make you think of cyclophosphamide toxicity.
Adenovirus infections in the very immunocompromised can also be bloody; they are
now treatable with antivirals.
* Future pathologists: You'll learn to recognize "cytoxan cells",
which have big hyperchromatic nuclei and scanty cytoplasm, but smudgy
nuclear chromatin that lets you know they're not cancer.
Review of the histopathology of chemotherapy cystitis: Am. J. Surg. Path. 28: 909, 2004.
A marked increase in mast cells showing signs of activation
(J. Urol. 163: 1009, 2000; this is now a robust finding and basis
for experimental therapies.) Stain with tryptase.
{24004} malakoplakia, Michaelis-Gutmann bodies
{25280} cystitis cystica, histology
{24007} cystitis glandularis, histology
Von Brunn's nest, cystitis cystica,
and cystitis glandularis
Adami & McCrae, 1914
.
This is a terrible public
health problem, and the bladder can be ruined by all the eggs in the detrusor.
Having a catheter in the bladder for a long time can cause protective
squamous metaplasia of the urothelium. Squamous cell carcinoma has been
an under-recognized problem in these people (J. Urol. 161:
1106, 1999.)
Have you ever read about comedian
Roscoe "Fatty" Arbuckle and the coca-cola / champagne bottle (or whatever)?

Mr. Arbuckle
{25307} amyloidoma, histology (including congo Red)

{21029} urothelial carcinoma, gross
{08858} urothelial carcinoma, histology
{08859} urothelial carcinoma, histology
{08860} urothelial carcinoma, histology
{08861} urothelial carcinoma, histology
{17200} urothelial carcinoma, histology
{17202} urothelial carcinoma, histology
{23987} urothelial carcinoma, histology
{24019} urothelial carcinoma, histology
{24082} urothelial carcinoma, cytology
{24083} urothelial carcinoma, cytology
{10034} urothelial carcinoma, cytology
{10040} urothelial carcinoma, cytology
Bladder carcinoma in situ
Very anaplastic, no invasion
KU Collection
Urine cytology
Normal and cancer
Wikimedia Commons
Naming urothelial tumors is confusing and aggravating because no one truly knows
the natural history of lesions that are always removed as soon
as they are discovered, and where it isn't really possible to tell a recurrence
from a second primary (and 70% of survivors will get a second
urothelial primary).
Hence, there have been several different systems
of nomenclature, and certain lesions that are "benign" in some
are "malignant" in others.
The flat lesions typically have loss of RB1 and p53.
THE FLAT LESIONS are most likely to present with discomfort,
if they are symptomatic at all. The reason for this is that the integrity
of the epithelial barrier is somewhat compromised, and salty urine
contacts the nerves of the mucosa. (Remember how much potassium hurts
when it contacts an exposed nerve?)
Flat urothelium:FLAT UROTHELIAL HYPERPLASIA is said to be present when it
is "flat and >7 cells thick" (i.e., there are
more than 7 layers of nuclei, some say 8 -- remember that of course the nuclei
aren't really layered, and that a tangential
cut will make there appear to be more).
UROTHELIAL CARCINOMA IN SITU of the bladder features
obviously anaplastic cells in a flat
urothelium.
REACTIVE UROTHELIAL ATYPIA will be diagnosed when the pathologist
recognizes nuclear changes of rapid epithelial regeneration
(i.e., big nuclei, marginated chromatin, and obvious nucleoli) without
any sign of anaplasia. Usually the number of layers is still normal
Of course, this means there's been instrumentation, or a stone,
or an infection, or whatever. This has no premalignant potential.
Of course, this is probably premalignant. You watch these patients.
There may be full-thickness, obvious anaplasia. In this case, the urothelium
actually tends to be thin, and the cells tend to come apart.
A variant is the INVERTED PAPILLOMA ("Brunnian adenoma"), a smooth-surfaced
bump with
epithelium complexly infolded deep within it. ("A glove with the fingers
pushed inside and collapsed.") There is no atypia, no desmoplasia,
and there's a good top layer to the epithelium. So it shouldn't be mistaken
for cancer.
* The PUNLMP remains controversial and accounts vary widely, perhaps
from inter-observer variability. For an update, see
J. Urol. 175: 1995, 2006.
You'll learn the new staging systems on rotations.
One of the common tough calls in pathology is, "Is this papillary
urothelial carcinoma of the bladder still confined to the
epithelium (Ta) or down into the lamina propria (T1)?"
* Immunohistopathology helps make the hard calls.
Carcinoma in situ is likely to stain for p53 and/or
cytokeratin 20,
and to have a high division index as shown by MIB-1 / Ki-67.
Also watch ErbB-4; staining for this oncogene product
is an ominous sign (J. Urol. 179: 353, 2008).
smoking (2-4x base risk)
Patients with superficial bladder
cancer usually do well, especially with today's treatment, which often
includes intravesical BCG. PROGNOSIS in invasive
urothelial carcinoma depends on grade-and-stage (correlate pretty
well most of the time). For the less-ugly, low-stage cancers, prognosis correlates
with other markers of malignancy, including loss of ABO antigens (* demonstrated
by some of your lecturer's Chicago friends), aneuploidy, and activation of known
oncogenes.
You need to know of a few other bladder tumors.
One arises from where the urachus used to
be, high on the front of the bladder. The prognosis depends mostly on stage (Cancer 110: 2434: 2007).
.
This is the great cancer menace in
Egypt, and it is extremely aggressive and lethal. Even a significant amount
of real squamous metaplasia in a urothelial carcinoma is ominous.
The treacherous lesion is positive for the famous prostate cancer marker AMACR, and often
prostate-specific antigen as well. Future pathologist beware!
I peed in the Rhine. --George S. Patton
Marginal note, March 1945

* SLICE OF LIFE REVIEW
{14938} ureter (cross section), normal
{14939} ureter (epithelium), normal
{14940} urinary bladder, normal
{14941} urothelium, normal
{15032} urethra, normal
{15033} urethra, normal
{15108} ureter
{15109} ureter
{15111} ureter
{15112} ureter
{15113} bladder, urinary
{15114} bladder, urinary
{15119} bladder, urinary
{15120} bladder, urinary
{15122} bladder, urinary
{15325} ureter, normal
{15326} bladder, normal
{15327} bladder, normal
{15588} bladder, normal
{15771} bladder normal unfixed, inner surface
{15772} bladder normal unfixed, inner surface
{20930} urethra
{20931} urinary bladder
{25172} urethra, normal
{25174} urethra, normal
{25266} bladder, normal
Pathology of the Urinary Bladder (Major Problems in Pathology series)
Pathology of the Urinary Bladder (Major Problems in Pathology series)
Robbins and Cotran Pathologic Basis of Disease
Rosai and Ackerman's Surgical Pathology
Rubin's Pathology: Clinicopathologic Foundations of Medicine
Silverberg's Surgical Pathology
| Visitors to www.pathguy.com reset Jan. 30, 2005: |
Ed says, "This world would be a sorry place if
people like me who call ourselves Christians
didn't try to act as good as
other
good people
."
Prayer Request
Teaching Pathology
If you have a
Second Life
account, please visit my teammates and me at the
Medical Examiner's office.
PathMax -- Shawn E. Cowper MD's
pathology education links
Ed's Autopsy Page
Notes for Good Lecturers
Small Group Teaching
Socratic
Teaching
Preventing "F"'s
Classroom Control
"I Hate Histology!"
Ed's Physiology Challenge
Pathology Identification
Keys ("Kansas City Field Guide to Pathology")
Ed's Basic Science
Trivia Quiz -- have a chuckle!
Rudolf
Virchow on Pathology Education -- humor
Curriculum Position Paper -- humor
The Pathology Blues
Ed's Pathology Review for USMLE I
![]() | Pathological Chess |
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Taser Video 83.4 MB 7:26 min |
