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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.
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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.
pathology.org -- my cyberfriends, great for current news and browsing for the general public
EnjoyPath -- a great resource for everyone, from beginning medical students to pathologists with years of experience
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.
During the fifteen 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!
Hypospadias Distinguish priapism from a normal erection, explain why it can be serious,
and mention some illnesses and how they cause priapism.
Describe how infectious urethritis occurs, and briefly describe reactive arthritis.
("Reiter's").
Describe the range of HPV-induced and syphilis-induced
pathology in the male. Give an account of squamous cell carcinoma
of the penis, and its various precursor lesions.
Tell what a general physician needs to know about cryptorchidism, epididymitis,
orchitis, and torsion.
Recognize each of the common germ cell tumors microscopically, and
describe their gross appearances, frequencies, known risk factors, markers, and
behavior. Recognize and describe Leydig cell adenomas and testicular
lymphomas.
Tell what can cause pain in the prostate. Give accounts of bacterial
and nonbacterial prostatitis.
Tell what we know about the etiology, pathogenesis, pathophysiology,
anatomic pathology, and consequences of prostatic hyperplasia.
Describe adenocarcinoma of the prostate in terms of its etiology, pathogenesis,
markers, anatomic pathology, patterns of growth and spread,
and clinical diagnosis, including the use of the lab.
Read a prostate needle biopsy, distinguishing cancer from the other
common lesions, and do simple grading of adenocarcinoma.
Use your pathology knowledge, along with your knowledge from other
lectures in this unit, to help answer common individual
patient questions in the primary
care setting.
QUIZBANK Men's problems (all)
I used to pray, "Lord, give me chastity, but not yet!"
A man should definitely get married. If it's a good
marriage, he will be happy. If it's a bad marriage,
he will become philosophical.
{47692} index identifies this as "human male"
Even where there is no mensch, strive to be a mensch.
--"Baghdad Betty", Iraqi disk jockey, during the first Gulf War
Love, who is fairest among the immortal gods,
HYPOSPADIAS: Abnormal opening of the urethra onto the ventral surface of the penis or scrotum.
This results from failure of fusion of the urethral folds, i.e., it is a form of feminization.
* And of course there are a host of statistical differences in other hormonal
levels between these youngsters and their normal counterparts, including
high-levels of mullerian inhibiting substance (J. Urol. 168: 1784, 2002).
Wherever the opening occurs, a fibrous band (chordee) distal to it will cause ventral curvature of the
erect penis.
There is often associated cryptorchidism, ureterovesical reflux, inguinal hernia, and/or other
developmental problems (J. Postgrad. Med. 37: 140, 1991).
A massive review of the anatomy: J. Urol. 160: 1108, 1998.
In the late 1990's, a "green" claim was presented to the public to
the effect that
hypospadias has doubled in frequency in the past twenty years,
and the cause is chemical pollutants acting as "endocrine disruptors", after
an initial CDC report seemed to spot a trend (Pediatrics 100: 831, 1997).
There was a huge hoopla and a bunch of studies.
All confirmed there's no increase in either incidence or repair rates
(Urology 57: 151, 2001; Env. Health Perspect. 108: 463, 2000; Pediatrics
115: e495, 2005; Arch. Dis. Child. Fetal-Neo. 89: F149, 2004).
In the old days, many children with the birth defect were simply not placed
in registries as they are today. The "green" claim that DDT is the
cause also fails under examination: Env. Health. Perspect. 113: 220, 2005.
Even Greenpeace has finally dropped these claims from their website (2008).
EPISPADIAS: Abnormal opening of the urethra on the dorsal surface of the penis.
Epispadias is actually a form of exstrophy of the urinary bladder. There is usually an associated
separation of the pubic bones and inadequacy of the urinary sphincters. Incontinence and bladder
infections are usual. There are many variants (J. Urol. 141: 903, 1989).
Epispadias is less common than hypospadias and more difficult to correct surgically.
PHIMOSIS: Present when the prepuce cannot be retracted over the corona.
Phimosis may be congenital, the orifice of the prepuce being too small.
More often, phimosis is due to poor hygiene, resulting in chronic inflammation and scarring, which
sets up a vicious cycle requiring circumcision.
Such an ongoing infection of the glans and prepuce is called BALANOPOSTHITIS. Many organisms may
participate. All about it: Urol. Clin. N.A. 19: 143, 1992. {24987} balanitis
PARAPHIMOSIS results when a tight foreskin is forcibly retracted, and edema of the glans prevents its
replacement. This can quickly lead to acute urinary retention and even gangrene of the glans.
PRIAPISM: A persistent, non-pleasurable erection (Mayo Clin. Proc. 72: 350, 1997;
Urol. Clin. N.A. 28: 391, 2001).
* "Priapus" was the classical-era Greek god of erections, but priapism is no joke.
Most cases of priapism are probably due to obstruction of the deep dorsal vein of the penis.
Typically the corpus spongiosum is uninvolved (i.e., the urethra and glans stay limp).
Causes include sickle cell disease (J. Urol. 145: 65, 1991), black widow
spider bite (famous; Pediatrics 114: e128, 2004), leukemia, metastatic cancer, papaverine
treatment of impotence (rare), and trauma (J. Urol. 148: 380, 1992); many cases are "idiopathic"
(i.e., something is causing abnormal thrombosis).
URETHRITIS
GONORRHEA and "NON-GONOCOCCAL URETHRITIS" ("urethral syndrome", due to
chlamydia Nowadays, it's a simply matter to check first-stream urine for DNA from
researchers to check for known pathogens.
One group checked for gonorrhea, Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma parvum and
urealyticum, herpes 1 and 2, adenovirus, and Gardnerella -- but for some reason
not for trichomonas (known to be an important cause -- J. Inf. Dis. 188:
465, 2003).
There's plenty of urethritis due to each bug in the study. Men tend to get herpes 1 and
adenovirus from oral sex (especially from other men), and most of the others from
unprotected vaginal sex with women. and there's at least one
unknown entity transmitted by oral sex.
Update on all this in J. Inf. Dis. 193: 336, 2006.
REACTIVE ARTHRITIS (formerly "Reiter's syndrome"): the enigmatic triad of (1) arthritis involving many joints, (2) conjunctivitis, and
(3) urethritis (for this handout, anyway) following a bacterial infection.
It's most familiar as a man's disease after sexually-transmittted urethritis, and lasts for several months.
Update Am. Fam. Phys. 60: 499, 1999.
The urethritis is usually
chlamydia When triggered by a gut infection, it's often salmonella, shigella,
campylobacter, or yersinia.
As with other "reactive arthropathies",
there's an impressive proliferation of T-cells specific for
chlamydia (when it's the cause) within the affected joints (Arth. Rheum. 34: 588, 1991).
Most patients are positive for HLA-B27.
Patients with reactive arthritis syndrome are likely to have circinate balanitis (red filagree rash on the glans), keratoderma blennorrhagica (hard bumps)
of soles, ulcers of the mouth, iritis, or even ankylosing spondylitis ("poker-back").
Before assuring a guy his urethritis "must be due to chlamydia" (because his gonococcal culture
came back negative), ask whether he eats lots of those little Mexican peppers. The hot chemical in
these can and does cause a urethritis.
There are a host of other reactive arthritis syndromes.
With more effective treatment for chlamydial urethritis, discussions
of reactive arthritis secondary to urethritis (classic reactive arthritis) are becoming few.
Christopher Columbus's arthritis-and-red-eyes was likely due to reactive arthritis: Am. J. Med. Sci. 332: 123, 2006.
* Hans Reiter described "Reiter's" in 1916 as reactive arthritis
following diarrhea rather than urethritis. He went on to become
one of the Buchenwald concentration camp "experimenters". This is one of the few eponyms
I prefer not to use.
PEYRONIE'S DISEASE: Proliferation of dense fibrous tissue involving a portion of the fascia.
This leads to curvature of erection. * Other names: "painful erection in the wrong direction", "squint
of the cock" (Osler).
This is one of several abnormal hyperplasias of fibrous tissue that
are sometimes called
"fibromatoses": another common one is palmar fibromatosis (Dupuytren's contracture of the hand)
which often occurs with Peyronie's disease. Photomicrographs: J. Urol. 157: 282, 1997.
* Metaplastic ossification and calcification are common.
The etiology is completely obscure. Trauma as a possible
cause: Yes (J. Urol. 158: 1388, 1997); no (J. Urol. 172: 186, 2004).
Treatment for Peyronie's disease is not very satisfactory, and many patients eventually require a
penile prosthesis.
New procedures: J. Urol. 167: 2066, 2002.
Natural history of Peyronie's: J. Urol. 144: 1376, 1990.
{25287} Peyronie's, histology
WARTS: There are two common "warts" involving the penis:
CONDYLOMA ACUMINATUM ("pointed knob"): a papillary, keratinizing lesion caused by the
sexually-transmitted "human papilloma virus" (usually strain 6). In males, it commonly occurs in
the urethral meatus, which is perhaps the worst possible location (why?)
To spot HPV involvement, wet the man's external genitalia with acetic acid ("* sheep dip") and
involved areas show white ("acetowhite", as on the uterine cervix). It's now called "androscopy"
(J.F.P. 29(3): 286, 1989). See J. Urol. 143: 920, 1990 for a discussion on criteria for diagnosing
HPV histologically on biopsies of acetowhite areas. All about the histopathology of HPV, warts and
men: Arch. Derm. 128: 495, 1992.
We have lots of ways of dealing with these warts, ranging from electrocautery and lasers to
interferon and fluorouracil (Postgrad. Med. 86: 197, 1989, by my friend Dr. Ila Peterson). It's
important to treat both partners, since this reduces reinfection.
{24460} condyloma, gross
{25098} condyloma, histology; note HPV-effect (shrunken, wrinkled nuclei, perinuclear halo)
CONDYLOMA LATUM ("flat knob"): groups of flat-topped lesions that
may ooze serous fluid; caused
by secondary syphilis GENITAL HERPES
PEARLY PENILE PAPULES ("PPP on the pp") aren't warts at all, but little bumps, sometimes hairy, which pop up in young
adults, especially on the corona.
Each is a single big dermal papilla. No need to treat.
About one man in 100 has them, and I get a very large number of questions
from visitors to my site. I point out they can be considered a "plus".
CANCER OF THE PENIS: Almost all are variations on squamous cell carcinoma (histopathology:
Urol. Clin. N.A. 19: 227, 1992; review South. Med. J. 87: 848, 1994).
This is a disease of older men, and it originates on glans and prepuce.
Only 1% of cancers among American men begin on the penis; the figure is as high as 18% in the
Orient.
Risk factors include phimosis, smegma, and balanoposthitis. However, by far the strongest risk is
infection with HPV, notably HPV-16. The other risk factors seem to create the fertile soil where
Nowell's Law can operate.
Good reading: Cancer of the penis is the second most-common male cancer, and cancer of the cervix
the most common female cancer, on the island of Bali, where the men are uncircumcised and
unhygienic, and both cancers are strongly HPV-linked (Cancer 64: 559, 1989).
Males circumcised as infants almost never get cancer of the penis. The incidence is much lower in
those circumcised at a later age than among the uncircumcised.
The basaloid variant, which usually arises on the glans, is quite anaplastic
and very aggressive; by contrast, the verrucous variant
has very little propensity to metastasize (J. Urol. 176: 1431, 2006.)
The papillary and condylomatous are also rather tame.
Today's patient is likely to be offered laser therapy instead of surgery
(J. Urol. 169: 2118, 2003). Mohs' microsurgery seems effective: J. Urol. 178:
1980, 2007. Carcinoma of the penis spreads to the inguinal lymph nodes. Five year survival is around 50%
overall.
{46450} squamous cancer of the penis, metastatic to the head
PREMALIGNANT LESIONS OF THE PENIS
ERYTHROPLASIA OF QUEYRAT: A raised, velvety plaque on the uncircumcised glans or prepuce.
Histologic study shows dysplasia of the squamous epithelium.
The term "erythroplasia of Queyrat" seems to be passing out of use.
Historically, it's been used for not-very-anaplastic
squamous carcinomas in situ on the glans, while Bowen's includes the more outrageously
anapastic ones located anywhere (penis or elsewhere). We treat them the same.
* Treatment has historically been with topical 5-fluorouracil,
whether patients are HPV-positive or negative. Imiquimod (the immune-modulator
widely used nowadays in dermatology) also seems to work (J. Am. Acad. Derm. 55:
901, 2006).
A minority of cases (5-30%, estimates vary) develop into squamous cell carcinoma if not removed.
{25095} erythroplasia of Queyrat, gross
BOWEN'S DISEASE: Carcinoma in situ of the skin, most often on the penis or scrotum in men.
Look for individual very weird cells with lots of mitoses.
Some cases (maybe 10%) develop into invasive squamous cell carcinoma.
* There is a popular claim that
the appearance of Bowen's disease on the skin heralds the growth of another
malignancy internally. I am not aware of any reason to believe this is true.
BOWENOID PAPULOSIS: Multifocal intraepithelial neoplasia, caused by HPV-16. The atypia
is mild.
* Future pathologists: Bowenoid papulosis tends to spare the hairs
and involve the sweat glands. Bowen's disease tends to spare the sweat
glands and involve the hairs.
Giant condyloma of Buscké-Lowenstein, or VERRUCOUS CARCINOMA: Another HPV-related, very ugly
cauliflower-like lesion. (See Arch. Derm. 126: 1208, 1990; J. Urol. 141: 950, 1989). Invasive
cancer can breed here.
{25101} verrucous carcinoma, gross
A standing army is like a standing member. It's an excellent
assurance of domestic tranquility, but a dangerous temptation
to foreign adventure.
I never trust a man unless I've got his pecker in my pocket.
When we've got them by the balls, their hearts and minds will follow.
MALE INFERTILITY
Leave the pathology of these problems to specialists. Male infertility (i.e., she's fertile, and they've
been trying without success for a year) has a variety of causes, known (Down's, Klinefelter's, old
torsion, old mumps Spermatogenesis can be temporarily diminished or even stopped by a host of factors ranging from
heavy drinking to anabolic steroid abuse to bicycling.
Obstruction of the sperm passages (can you think of etiologies?) may be more amenable than the
above to surgical help. Or a sperm can be obtained by aspiration from the testis in order
to fertilize an egg.
Many men without obstruction have maturation arrest of spermatogenesis; especially
when this is uniform, the man is likely to harbor a genetic abnormality (often a microdeletion on the
Y-chromosome), and is unlikely to be a father by any means (J. Urol. 178: 608, 2007).
The pesticides DBCP (dibromodichloropropane, "Nemagon") and chlordecone
do cause infertility in men, by preventing the sperms
from differentiating. This has been known since the 1950's, and the
fact that companies still used them overseas after they were rightly
banned in the US is all-too-typical. The rat model, and an easy way to restore
their fertility: Tox. Sci. 76: 418, 2003.
{00086} testicular atrophy, no sperms
* Some guys ("fertile eunuchs", a misnomer) just don't make LH, and may or may not make FSH.
They become fertile if you replace the gonadotropins.
* Evaluation of the azoospermic patient, by Jon Jarow MD,
a lifetime friend of your lecturer: J. Urol. 142: 62, 1989. He's
also reviewed anabolic-steroid induced hypogonadotropic hypogonadism: Am. J. Sports Med. 18:
429, 1990.
Slow-learner guy with large testes: Fragile X!
CRYPTORCHIDISM (cryptorchism): Incomplete descent of the testis into the scrotal sac.
Review Am. Fam. Phys. 62: 2037, 2000.
Unilateral or bilateral cryptorchidism occurs in around 4% of prepubertal boys. (Maybe 1 boy in 10 is
born with at least one not fully descended, but the majority do descend in the first year.)
Cryptorchid testes
may be found anywhere along the normal route of descent (abdomen, inguinal canal, prepubic).
Occasionally a testis that is present in the scrotum at birth may retract
back into the abdomen (or have the cord fail to grow as the boy
does: J. Urol. 157: 1892, 1997);
this is also cryptorchidism and has the same associated risks and basically
the same histology: J. Urol. 162: 878, 1999.
The epididymis is likely to be malformed or at least elongated. See J. Urol. 143: 340, 1990.
Some centers biopsy each testis at the time of surgery, and
administer gonadotropin releasing hormone if the histology shows very few
germ cells per tubule (read about it J. Urol. 169: 659, 2003).
ECTOPIC TESTIS is less common; it may stray into the superficial inguinal region, penis, or femoral
sheath.
Failure of the testes to descend into the scrotum causes problems:
In 1989, 300 brave Danish men who had been treated for cryptorchidism consented to needle
biopsy; 5 had carcinoma in situ and 2 other had already been treated for testicular cancer (J. Urol.
142: 998, 1989).
Most cryptorchidism is idiopathic. It may be accompanied by other developmental abnormalities,
diethyl-stilbestrol exposure, and poorly-understood anatomic and hormonal problems.
EPIDIDYMITIS AND ORCHITIS: Ouch!
NONSPECIFIC INFECTIONS of the contents of the scrotum are usually complications of urinary tract
infection, instrumentation (for example, clean-intermittent catheterization: Eur. Ur. 22: 53, 1992),
or prostate surgery.
GONORRHEA: the infection often spreads to the epididymis, less often the testis.
{40116} abscess of the epididymis, gonococcal I'd bet; the tan structure with the white rim is a
cross-section of testis
MUMPS TUBERCULOSIS {25221} tuberculosis of epididymis
SYPHILIS TORSION OF SPERMATIC CORD ("torsion of the testis"): Am. Fam. Phys. 74: 1739, 2006
Twisting of the spermatic cord is likely to result in venous infarction and gangrene in a few hours.
This is quite common, especially in children and adolescents.
Spasm of the cremaster muscle keeps the process going (pain spasm pain cycle). The involved testis
is painful and elevated; the cord is typically twisted 540 degrees.
There may or may not be a history of trauma (often minor, as in baseball or break dancing; see
JAMA 256: 3366, 1984).
The underlying problem may be abnormal fixation of the testis or cryptorchidism. Ask a urologist
about the "bell clapper" deformity, with the tunica vaginalis running too high up the
spermatic cord. This supposedly results in torsion after intermittent episodes of
testicular pain (J. Urol. 148: 134, 1992). Of course, once the process
starts, spasm of the cremaster
muscle still plays a role.
You, the physician, may be able to untwist the cord manually. If not,
emergency surgical intervention is indicated. You'll learn about the diagnostic pitfalls
(imaging studies can be unreliable, etc.) on rotations.
An old infarcted (hyalinized) testis is a common surprise finding in autopsy series -- suggesting that
the diagnosis of torsion is often missed.
More seriously, unilateral spermatic cord torsion can somehow damage the opposite testis. Nobody
knows how this happens (J. Urol. 144: 366, 1990); reflex vasoconstriction? autoimmunity?
Torsion of the appendices of the testis and epididymis are painful but not so serious.
A person can also suffer loss of one testis by catching it in a hernia. (There's no room here to talk
about hernias!)
* As noted above, after unilateral torsion of a testis, there is some increase in risk
of infertility even though there was never damage to the other testis.
No one understands the reason; a group
of men who had survived torsion underwent contralateral
biopsy and all had some increase in apoptosis of the germinal
cells (J. Urol. 160: 1158, 1998).
{10892} torsion, gross
Scrotal squamous cell carcinoma is the subject of the famous chimney sweep story.
FOURNIER'S GANGRENE is a synergistic bacterial infection that produces the dreaded
"black sack disease" (no joke; most common
in debilitated individuals; huge review
Br. J. Surg. 87: 718, 2000).
Many older men
get a few angiokeratomas (hemangiomas with each dermal papilla
stretched wide by a single ectatic blood vessel), especially on their scrotums, and this doesn't mean Fabry's.
About 95% of tumors of the testis are malignant germ cell tumors.
It is now clear that the cells of origin of the "germ cell tumors"
really are the germ cells.
In adults (but not in children, and not in spermatocytic
seminoma), the in situ lesion
INTRATUBULAR GERM CELL NEOPLASIA, UNCLASSIFIED
(IGCNU) can usually be identified in nearby seminiferous tubules (Arch. Pathol. Lab.
Med. 109: 555, 1985 for the original pictures).
The in-situ precursor is now easy to spot. IGCNU cells usually stain with placental alkaline phosphatase (PLAP),
cKit/CD117, p53, and OCT3/4 (the latter a seminoma / embryonal
cell carcinoma nuclear marker.)
Embryonal carcinoma in situ:
Arch. Path. Lab. Med. 126: 48, 2002. Microinvasive carcinoma: Cancer 70: 659, 1992.
We believe that most or all IGCNU will turn invasive if left alone, half within five years.
A German group examined sections from all males coming to autopsy, and
found that the prevalence of carcinoma in situ of the testis (6 out of 1388)
was good match for lifetime risk, i.e., it usually starts in situ, and the in situ lesion
usually turns invasive.
(J. Urol. 173: 1577, 2005)
See below.
Almost all germ cell tumors of the testis
present as painless, non-tender masses in the testis.
The primary may be occult, especially if it's a pure choriocarcinoma.
Many cause gynecomastia (after puberty) or precocious puberty (children.)
Today, the diagnosis is usually obvious based on tumor markers and/or
ultrasonography; only rarely is biopsy necessary before radical orchiectomy.
Urologists have special procedures for difficult cases, especially
bilateral disease in the man wishing to preserve natural fertility.
Sometimes the opposite testis is
biopsied in a search for carcinoma in situ. These protocols will
change by the time you are in practice.
Risk factors for this disease are poorly understood. They include cryptorchidism and some intersex
malformations (Arch. Path. Lab. Med. 114: 679, 1990).
There are some familial cases (Mayo Clin. Proc. 65: 804,
1990) but if there is an anti-oncogene syndrome, it remains elusive.
Other risk factors are earlier puberty, and supposedly
lack of exercise as a kid.
Today's boys have both,
compared to us men who are now middle-aged, and this is probably why cancer of the testis is
becoming significantly more common around the world: Br. Med. J. 308: 1393, 1994;
J. Urol. 170: 5, 2003; mostly seminomas in the US: Cancer 97: 63, 2003.
* Your lecturer is also unimpressed with a retrospective study of
showing that admitting to being a marijuana smoker gives a 1.7x risk for
testicular cancer (Cancer 115: 1215, 2009). It seems "recall bias"
would be operating -- young men upset about
having cancer are more likely to 'fess up to smoking a joint from time to time.
Cancer in a testis confers approximately 50x increased risk of there
being at least carcinoma in situ in the opposite
testis. No one really knows what to do about this fact: J. Urol. 160: 1353, 1998.
* Anti-Ma2 is an autoantibody most often seen in testicular cancer
patients that causes a brainstem and limbic encephalitis (can't move eyes, Parkinsonism,
stop talking;
Brain 127: 1831, 2004).
* Future pathologists: When you are handling a resected testis, please....
SEMINOMA (Cancer 64: 1608, 1989): cancer that closely resembles young spermatocytes.
Grossly these tumors are homogeneously soft and yellowish.
Tumor cells have "fried egg" appearance (* glycogen-rich cytoplasm);
arranged in masses separated by fibrous septa with a
lymphocytic infiltrate, may have syncytiotrophoblast and/or granuloma formation.
* Tumors with more than 30 mitotic figures per 10 hpf
have historically been considered more aggressive
(the old "anaplastic seminoma") but since cure rates are so high
nowadays, this is moot.
Chorionic gonadotropin (hCG) is a tumor marker for the 20% or so of seminomas that contain
syncytiotrophoblast (i.e., the man has a positive pregnancy test). * You may be told this is a bad
prognostic indicator but this is probably not important (J. Urol. 151: 67, 1994).
Seminomas typically metastasize to the retroperitoneal lymph nodes and then to the lungs.
Seminomas are remarkable for their good response to radiation or chemotherapy as appropriate, and
even widespread disease can usually be treated with five-year survivals of 95% or better.
* The traditional wisdom is that two years following complete remission, the patient can probably consider himself cured.
Later recurrence of seminoma is uncommon but does occur: Cancer 95: 520, 2002 (many of these
are the people who have apparently benign teratomas left behind.)
Tumors with histology and response to therapy like testicular seminomas (or other germ cell tumors)
also arise in other midline structures including the retroperitoneum, thymus, and pineal
("germinomas"), as well as in the ovary ("dysgerminoma").
* Watch the new tumor marker SALL4, which is reported to be
very sensitive and specific for germ cell tumors. Especially if you
run into a metastatic tumor of unknown primary, knowing this is of germ
cell origin is a marker for curability (Cancer 115: 2640, 2009).
The cells
bear a typical nuclear chromatin pattern looking
like the stuck-for-days-unwinding pattern
of normal spermatocytes.
* Unlike true seminomas, staining for OCT3/4 and PLAP are negative.
There's also usually no glycogen and no lymphocytes
It almost never metastasizes "as itself", but about 5%
transform into some sort of sarcoma (Cancer 61: 409, 1988) and can metastasize
as such.
EMBRYONAL CELL CARCINOMA: a very primitive cancer that arises in the testis.
Grossly these are grayish-white masses with hemorrhage and necrosis. Microscopically, the tumor
cells grow in sheets, knobs, etc.
Future pathologists: distinguish from a seminoma by absent glycogen
and positive staining for cytokeratin (seminomas are usually weak or negative).
OCT3/4 is usually positive, D2-40 is negative, PLAP is usually positive,
and Ki-1/CD30 is usually positive in embryonal carcinomas
but negative in other germ cell tumors.
If the tumor seems to be stage I, metastases are much
more likely if there is vascular invasion seen in the primary; the pathologist
will note this on report.
{23954} embryonal cell carcinoma, lumen of some kind and some wilder stuff
Many embryonal cell carcinomas also contain differentiated structures of
a teratoma. (Teratoma +
embryonal cell carcinoma = TERATOCARCINOMA).
{25401} teratocarcinoma
Tumor markers for common mixtures that include embryonal cell carcinoma include hCG (from
trophoblast areas), α-fetoprotein (AFP, from yolk-sac areas), and * lactate dehydrogenase (LD,
LDH, which is nonspecific and probably of no value).
Tumors with an embryonal cell carcinoma component metastasize to the retroperitoneum and
everywhere else.
Metastases very often mature into benign teratomas during treatment.
It is now clear
that these are usually (but not always) benign, and that persistently elevated tumor markers
can be due to slow leakage from cyst fluid (J. Urol. 171: 168, 2004).
Do not overtreat. However, maybe 1 in 5 of these men do eventually
have the cancer recur (Cancer 115: 1310, 2009).
Or the cured metastases may turn into scar tissue, or just plain necrotic debris (J. Urol. 142: 1239,
1989).
The response to newer chemotherapy protocols is very good, with around 85% apparent cures even
when metastatic disease is widespread (Cancer 56: 2411, 1985).
* Most protocols are now based on ifosfamide and platinum. They are highly successful,
and the old retroperitoneal lymph node dissection procedure is now reserved
for hard cases. The pathology specimens are often curious,
with the tumors much altered by chemotherapy (Cancer 109: 528, 2007); any viable
tumor in the specimen is ominous (Cancer 107: 1483 & 1503, 2006).
The most infamous after-effect of the traditional
retroperitoneal lymph node dissection was the loss of the ability to ejaculate
(why?); see J. Urol. 142: 1487, 1989 and Cancer 64: 2399, 1989 for psychological well-being after
testicular cancer.
There's also a nerve-sparing retroperitoneal
lymph node dissection technique that supposedly leave the
ability to ejaculate intact (update J. Urol. 169: 1710, 2003). Some centers now use nerve-sparing surgery-only,
no chemotherapy (Urol. Clin. NA 25: 461, 1998).
Again, a two-year disease-free survival generally indicates cure.
CHORIOCARCINOMA:
The bloodiest solid tumor in pathology; solid areas may be hard to find.
The malignant cells resemble placenta, and the pathologist must identify cytotrophoblast and
syncytiotrophoblast. There are no villi.
HCG levels are always very elevated (serum, urine.)
Choriocarcinoma most often is a component in a teratocarcinoma, but may be pure or mixed with
any other germ cell tumor components.
Until recently, choriocarcinoma arising in the testis was always lethal.
Today the prognosis is not much worse than for embryonal cell carcinoma, even if the tumor is
"pure choriocarcinoma".
YOLK SAC TUMOR ("endodermal sinus tumor", "orchioblastoma", "infantile embryonal cell
carcinoma"):
The commonest testicular tumor of children (but still quite rare), usually occurs "pure" rather than
mixed with other germ cell tumor types. It is composed of papillary structures (Schiller-Duval bodies) with extracellular globs of
α-fetoprotein and α-1-protease inhibitor.
This carcinoma is also unusual because it metastasizes hematogenously.
Response to chemotherapy is very good in kids, and pretty good in adults.
DIFFUSE EMBRYOMA
has a layer of yolk sac tumor surrounding an embryonal cell
carcinoma, as if it were itself the amnion.
{25175} yolk sac cancer, gross
TERATOMAS:
Cystic teratoma of testis is rare (but common in ovary) and
seldom contains hair. (Teratomas are the only testicular tumors
that are often cystic.)
Solid teratomas are of two types:
Mature solid teratoma is benign, usually occurs in children.
Immature solid teratoma is malignant, usually contains embryonal cell carcinoma
(TERATOCARCINOMA)
or sometimes squamous cell carcinoma.
Even if an adult's teratoma appears altogether benign, there is likely to be nearby intratubular
carcinoma in situ (Cancer 64: 715, 1989). It's now generally
accepted that
"all testicular teratomas in adult men are best considered malignant", though of course
the presence of obvious cancer is obviously more ominous.
* Just to confuse things, the WHO has decided that a dermoid cyst (i.e.,
mostly inside-out skin but with three germ layers) and NO IGCNU nearby is benign
regardless of age.
However, since these are almost entirely children's lesions (which are benign), and very few are reported
from grown men, this seems questionable.
WARNING: Any tumor of germ cell origin may be mixed with any other tumor of germ cell origin.
Further, any tumor of germ cell origin may metastasize as another histologic type of germ cell
tumor (Am. J. Clin.
Path. 97: 468, 1992).
MALIGNANT LYMPHOMA arises in the testes of older men with some frequency.
Update Arch. Path. Lab. Med. 131: 1040, 2007; Am. J. Med. Sci. 336: 336, 2008.
They are the commonest testicular tumor of older men, and tend to be very aggressive,
recurring soon after initial treatment and proving refractory to further therapy.
ADENOMATOID TUMOR is a benign, hard spherical
nubbin, usually in the head of the epididymis,
derived from mesothelium (* positive for EMA, cytokeratin, calretinin was the final proof.)
They are quite common.
Germ-cell tumors (seminomas, embryonal cell tumors, teratocarcinomas, choriocarcinomas, and the
usual mixtures -- but not spermatocytic seminomas) can and do arise in the retroperitoneum, mediastinum, and pineal "because they are
midline structures" (?!). Their behavior is similar to testicular tumors. Review Chest 103-S4: 331-S, 1993.
* Famous testicular cancer victims include funmaker Tom Green
(non-seminoma), Olympic gold-medal swimmer
Alex Baumann, Russian writer Alexander Solzhenitsyn ("Cancer Ward", had seminoma),
cyclist Lance Armstrong (nonseminoma), figure skater Scott Hamilton
(non-seminoma), Chinese dissident Chen Ziming, football player Brian Piccolo ("Brian's song"),
runner Steve Scott, and more.
STROMAL TUMORS
LEYDIG CELL TUMORS: occur at any age, are usually benign, can produce precocious puberty or
gynecomastia. Update Arch. Path. Lab. Med. 131: 311, 2007.
The gross and microscopic appearances are typical for endocrine tumors. Sometimes, the
pathologist can make the diagnosis easy by identifying a Reinke crystalloid!
* Criteria for malignancy are necrosis, mitotic figures, local invasion,
and nuclear pleomorphism, just like you'd expect. MIB-1, the proliferation
marker, seems to be a powerful predictor (Am. J. Surg. Path. 22: 1361,
1998).
The tendency today seems to take the tumor and leave the testis behind,
as long as there's no suspicion of malignancy (J. Urol. 178:
507, 2007). A huge British study found NO sex-cord stromal (i.e., Sertoli / Leydig)
tumor to have metastasized in recent history (J. Urol. 181: 2090, 2009),
though the world literature contains references to this happening.
Sertoli cell tumors ("androblastomas"; Urology 25: 1985; Am. J. Clin. Path. 96: 717, 1991),
are uncommon.
Animal model Am. J. Path. 144: 454, 1994; Urol. Clin. N.A. 27: 529, 2000. Calcified sertolioma:
think Peutz-Jegher's.
* Future pathologists: The tumor marker for Sertoli-Leydig differentiation
is inhibin (Am. J. Surg. Path. 22: 615, 1998.)
HYDROCELE: Fluid in the tunica vaginalis. Usually idiopathic, a hydrocele may contain 100 cc
or more of serous fluid.
If ascites is present and the patient has a patent processus vaginalis, a hydrocele will appear and
disappear as the patient changes position.
You can distinguish a hydrocele from a tumor mass by trans-illuminating it with a bright flashlight
in a dark room.
* Today's man can choose between traditional surgery and sclerosing therapy.
{24589} hydrocele, gross
HEMATOCELE: Blood in the tunica vaginalis. May follow trauma (J. Urol. 127: 1195, 1982), or warn
of an underlying testicular cancer.
{25191} hematocele (guy got kicked probably)
VARICOCELE: Varicosities of the pampiniform plexus, usually on the left side (why?)
This is common in young men, may cause fertility problems by warming the testes.
A new varicocele in an old man often indicates occlusion of the vein by renal cell carcinoma,
especially if the veins do not collapse when the patient lies down.
SPERMATOCELE: a cystic lesion up to 1 cm or so in the area of the rete testis, filled with fluid and dead
sperms.
PROSTATITIS
Pathologists distinguish three types of acini. The mucosal and submucosal
are in the periurethral ("inner") zone, separated by smooth muscle from the external acini
("cortical" / "outer").
Acute and chronic prostatitis are uncomfortable problems, and are common in men who catch
sexually-transmitted urethritis or lower urinary tract infections.
E. coli is the most common etiologic agent of both acute and chronic prostatitis.
The diagnosis depends on physical and lab exams.
In acute prostatitis the gland is exquisitely tender. You should probably not attempt to express fluid!
Gonorrhea is an important cause of acute prostatitis (secondary to urethritis; remember it can also
cause epididymitis).
{25212} acute prostatitis, gross
In chronic prostatitis the gland is somewhat tender and the prostatic fluid you express contains
WBC's and grows bacteria.
Treatment is very difficult because of problems getting antibiotics to the bacteria.
{25214} chronic prostatitis, histology
In "non-bacterial prostatitis", the findings are as in chronic prostatitis (expect
white cells in the semen), but no organisms grow.
(Probably chlamydia "Prostatodynia" is a stress-related pain syndrome in which there are no WBC's in the prostatic fluid.
Other exacerbating factors include constipation, smoking, coffee, and spices (all of which make an
infected prostate hurt more, too. See Urology 26: 320, 1985.)
* "Prostatosis" is an old term for both non-bacterial prostatitis and prostatodynia.
Granulomatous prostatitis may be due to TB
Prostate infarcts, which produce hematuria and a painful lump,
usually result from instrumentation that causes arterial thrombosis.
* Squamous metaplasia in prostate epithelium occurs at the edges of infarcts, or in men treated with
estrogens or finasteride.
{23968} granulomatous prostatitis
* A curious fact about prostate pathology is that benign cysts are
common (and often seen on ultrasound), and may obstruct, but have never been
seriously studied or subtyped by pathologists. See J. Urol. 181: 647, 2009.
PROSTATIC HYPERPLASIA ("benign prostatic hypertrophy or hyperplasia", "BPH"). Review:
Disease-a-Month 41: 437, 1995; Urol. Clin. N.A. May 1995.
This is something that happens to most intact men over about age 50; 10% of men living to age 80
will need prostate surgery.
Surprisingly, there is remarkably little work on its basic biology.
The normal prostate weighs around 20 gm. Old men's prostates enlarge to 60-200+ gm.
The increased tissue is nodular overgrowth of periurethral glands and stroma. The hyperplasia most
often involves the lateral and median lobes.
Future pathologists: Look for expanded glands, often with papillary infoldings, and dense, stroma.
The low-power view proves that the overall architecture of the gland is preserved. All about the
histopathology: Urol. Clin. N.A. 17: 477, 1990.
There may be a preponderance of glandular hyperplasia, a preponderance
of stromal hyperplasia, or some of both.
* "Sclerosing adenosis", a fooler for cancer, has true myoepithlium
(S100 +, muscle-actin +), unlike cancer or common hyperplasia.
The site where the hyperplasia arises ("the transition zone") is well-characterized (Urol. Clin. N.A.
17: 477, 1990).
By contrast, "the posterior lobe is the most common site for the development of prostatic
adenocarcinoma". (* Do you think that this might simply reflect the fact that cancers here are easier
to detect early?)
Median lobe hyperplasia by itself produces a "median bar" (today, a "midline dorsal nodule"), obstruction without an enlarged gland.
Don't be fooled.
The etiology of prostatic hyperplasia is obscure. It probably has something to do with sex hormones
and their receptors. Heroic abstinence is also rumored to be a risk factor,
although probably for everybody else there's little
protection from more-frequent ejaculation (Urology 61: 348, 2003).
The most interesting work
focuses on various proteins produced by the
stroma that cause hyperlasia of glands, and proteins produced
by glands that cause hyperplasia of the stroma.
Long-studied, there are updates in
J. Urol. 172: 1784, 2004 and Endocrinology 146: 13, 2005.
There's a mouse model -- a transgenic mouse with its int-2 proto-oncogene (fibroblast growth
factor #3) revved up. It shows the same androgen dependency as do old men's prostates (J. Urol.
149: 633, 1993).
* Cell culture researchers talk about mysterious interactions
between epithelium and stroma (J. Clin. End. Metab. 83:
206, 1998.
Prostatic hyperplasia causes many problems (collectively called "prostatism"), though most patients
are asymptomatic.
The treatment is surgical -- one favorite procedure is trans-urethral resection (TURP), or try the
laser approach (J. Urol. 154: 174, 1995) or the newer cryosurgery
or microwave
techniques (pathology of cooked prostate: J. Urol. 171: 672, 2004;
also J. Urol. 170: 12, 2003).
Treatment
guidelines from the Feds: Geriatrics 49: 25, 1994.
I still think I'd opt for surgery rather than some of the
new hormonal manipulations.
Patients treated with 5-alpha reductase inhibitors (i.e., finesteride)
tend to get atrophy of the glands and some squamous metaplasia, but it is not spectacular.
The much-promoted saw palmetto fails a controlled study miserably: J. Urol. 171: 284, 2004;
another failure NEJM 354: 557, 2006.
{10743} prostate hyperplasia, gross. Don't try this paper clip trick at home.
Prostate cancer is the commonest cancer in men, and the second leading cancer killer of men. There are around
198,000 new cases in the US yearly, and 31,000 deaths (i.e., it's now our most common men's
cancer, but most of these men die of something else; see Lancet 1: 799, 1989).
This doesn't include LATENT PROSTATE CANCER (i.e., you found it only at autopsy, and it caused no
problems), and probably not all cases of INCIDENTAL
PROSTATE CANCER (i.e., you found it on the turp
chips). OCCULT PROSTATE CANCER might pop up in bone marrow or lymph node prior to becoming
symptomatic.
The tremendous increase in the incidence of prostate cancer during the 1990's
(about 30%) reflects the improved screening.
A man's lifetime risk of dying of the disease is
actually decreasing.
The in-situ lesion (formerly "prostatic dysplasia", now "prostatic intra-epithelial neoplasia")
was well-characterized
during the early 1990's (J. Urol. 149: 170, 1993; Am. J. Cln. Path. 96: 628, 1991). There's
always nuclear enlargement and crowding, there are usually nucleoli and some piling-up, and the
nuclei are more hyperchromatic as the grade increases. But there is no invasion or architectural
distortion. Low-grade "PIN" is common in young men (J. Clin. Path. 42: 383, 1989; J. Urol. 150:
379, 1993), and it probably takes decades to transform; most pathologists simply
don't report it even if they see it, and today's wisdom is that this is the correct
thing to do (J. Urol. 166: 402, 2001). The high-grade kind, distinguished by prominent nucleoli, is much
wickeder: J. Urol. 158: 12, 1997. Atypical prostate biopsies:
J. Urol. 159: 2018, 1998.
* Much of the work on this lesion was done by former
Mayo pathologist Dave Bostwick MD; I was his "path
resident" when he was a med student in 1978. I'm
proud of you, Dave!
Nobody knows yet exactly what to do when you
discover PROSTATIC INTRAEPITHELIAL NEOPLASIA
("carcinoma in situ" or whatever; update Arch. Path. Lab. Med. 131:
1257, 2007; pathologists see also J. Clin. Path. 60:
856, 2007). Usually these lesions will involve
part of a single sample. Nowadays, the feeling is that PIN3 requires
re-biopsy. Of course, we are going to assume that we are
not simply looking at an aggressive cancer spreading down the ducts,
which can look identical. Here's
how to make the call:
PIN3: As PIN2, but with prominent nucleoli and a papillary or cribriform pattern.
Today, the tendency is to call any PIN with ugly nuclei "high-grade PIN"
and merely subdivide into "tufting", "micropapillary", "cribriform", or "flat",
or not bother subdividing.
Any: The basal cell layer is at least somewhat intact. (It is NEVER
intact in true adenocarcinoma). Racemase / AMACR / P504S
is very often (some say almost always) positive in PIN.
Future pathologists beware: "Adenomatous hyperplasia" is an
mass of crowded glands, but without any nuclear abnormalities.
Best call it benign.
Prostate cancer is mostly a disease of men over age 50.
Prostate cancer is rare in Oriental folks in Asia, more common in Asian-Americans, common in U.S.
whites, and most common in U.S. Blacks.
The majority, but not all, prostate cancers supposedly
arise in the posterior lobe. Again, I wonder whether this merely reflects how much
easier these are to detect.
In classic studies, serial sections of prostates at autopsy show little adenocarcinomas in 10% or so of
US 50-year-old men and nearly 100% of 100-year-old men.
The most recent stuff is about the same (1 in 3 of men in their sixties,
about of half of men in their seventies: J. Urol. 179: 892, 2008).
Most are "occult", however. Today, some urologists will
advise patients to leave these alone if discovered (i.e., prostate-specific
antigen levels less than 15 ng/mL, Gleason 3+4 or less,
and a majority of cores negative on repeat biopsy after 18-24 months.
Update J. Urol. 178: 833, 2007).
Grade and volume determine metastatic
potential. Surprised? Of course not. And if the gland is clinically benign, the rate of metastasis
seems to be extremely low (or maybe even zero, Arch. Path. Lab. Med. 119: 731, 1995).
* How many turp chips should the pathologist check?
Most pathologists probably submit all the chips if they weigh
in aggregate 30 gm or less; at least one cassette for every 5 grams if more.
The etiology of prostate cancer is essentially unknown.
Androgens play some role; early castration prevents the development of adenocarcinoma (* not
worth it, though....)
There is probably no link to infection or prostatic hyperplasia, or to lack of sexual activity.
For some reason this was re-examined recently and the conventional
wisdom stands. Frequency of ejaculation does not seem to have any impact (good or bad)
on risk for
prostate cancer (JAMA 291: 1578, 2004).
Industrial exposure to cadmium (i.e., battery factories) is supposedly linked to increased prostate
cancer. (Everything bad about cadmium: Nature 361: 369, 1993.) The link
strongly disputed: J. Tox. 6: 227, 2003; J. Occ. Env. Med. 43: 593, 2001;
the animal model isn't striking Prostate 46: 11, 2001);
today most regulatory agencies don't classify it as a carcinogen.
A single major study links Agent Orange exposure in Vietnam to earlier
and more aggressive prostate cancers. Watch this one: Cancer 113: 2464, 2008.
An earlier study showed no link (J. Urol. 166: 100, 2001).
* Your lecturer suspects the old alleged "link" between vasectomy and prostate cancer simply reflects the
fact that men who get vasectomies go to the doctor more often, and get their prostates checked more
often. (See JAMA 269: 913, 1993).
The folks at the JAMA seem to consider the protective effects of tomatoes
to be established (JAMA 300: 33, 2008; from Mizzou); the question is now, "which molecules(s)?"
However, selenium and vitamin E, alone or in combination, totally
flopped as prostate cancer prevention in an enormous study (JAMA 301: 39, 2009).
There is a longstanding hoopla over high-fat / meat diet as a very important risk factor for cancer of the
prostate (Ann. Int. Med. 118: 793, 1993; update J. Urol. 171: S-19, 2004).
A huge study about carotenes, lycopenoids, etc., etc. and prostate cancer
turned up no correlation with overall risk
with some possible weak favorable correlations suggesting
protection against advanced disease
(lots of warnings against inferring cause and effect: Am. J. Clin. Nutr. 86: 672, 2007).
* Not so long ago there was a flap about milk consumption as being a risk factor.
The results are amazingly inconsistent (skim milk appears more
dangerous than whole milk: Int. J. Cancer 73: 634. 1997;
no no, it's the animal fat that's dangerous Br. J. Cancer 80: 107, 1999;
no it's the calcium and the effect is very small: Am. J. Clin. Nutr. 74:
549, 2001;
very weak link Int. J. Cancer 80: 704, 1999).
I can't really take this seriously when there so many confounding variables,
known and unknown.
I was more impressed with J. Urol. 154: 153, 1995; smokers don't have a higher rate of prostate
cancer, but the cancers are higher-grade and meaner.
* Molecular signatures that actually matter
to the prognosis or easy diagnosis remain elusive (J. Clin. Path. 58:
67, 2005). The only one so far that is typcially overexpressed in prostate
cancer regardless of grade, and not in benign prostate lesions, is PAX2
(J. Urol. 165: 2115, 2001). Expression of
survivin, an apoptosis inhibitor, seems to predict poor
prognosis: J. Urol. 171: 18855, 2004.
The tumor loses its androgen sensitivity when
(Nowell's law!)
the androgen receptor gene mutates
(no surprise, NEJM 332: 1440, 1995).
The best-studied prostate cancer gene is HPC1 / RNASEL, where a single
nucleotide substitution increases risk but apparently not aggressiveness (J. Urol. 179:
1344, 2008).
There is another prostate-cancer-family gene: HPC2 / ELAC2; curiously, it gives only about double the normal risk.
The same's true of each of five newly-identified loci
(NEJM 358: 910, 2008.
Not surprisingly, the high-grade cancers tend to stain for telomerase
and the low-grade ones don't (why?; Cancer 95: 2487, 2002).
Cancer of the prostate presents as a painless lump in the gland.
These tumors are easier to feel than to see; they are firmer than hyperplastic nodules, poorly
circumscribed, and yellowish.
Diagnosis is by biopsy or fine-needle aspiration. Or it may turn up in a routine prostatectomy
specimen. (If you're going to operate for obstruction anyway, there's no reason to biopsy first.)
Future pathologists: With all these guys getting needle biopsies nowadays, you need to try to find
tiny cancers. You must section several levels of the core biopsy (Am. J. Clin. Path. 107: 26, 1997;
Arch. Path. Lab. Med. 122: 833, 1998).
Prostate biopsies are tiny. In around 5% of them, the pathologist
is likely to ask for re-biopsy. Arch. Path. Lab. Med. 123: 687, 1995.
Help with your tough calls: Arch. Path. Lab. Med. 124: 98, 2000.
Recently, the trend has been to get lots of cores; ten is now commonplace
and twenty may become standard (J. Urol. 179: 504, 2008).
And by the way... the more prostate biopsies you get (at least if you're being
followed for a known cancer by "active surveillance"), the more likely you are
to get erectile dysfunction (J. Urol. 182: 2664, 2009).
When given a metastasis from a suspected primary, the pathologist stains for prostatic acid
phosphatase and/or prostate-specific antigen -- both are highly sensitive and specific for prostatic
origin.
Almost all are "prostate type" adenocarcinomas. (I find the traditional distinction
between "large duct" and "small acinar" to be less-than-helpful.)
To diagnose prostate cancer, you want to see one or more
of the following:
* Nuclei with sharp angles, and cytoplasm with vacuoles, suggests
that your "worrisome single-layered" acinus is benign basal cells, with the secretory
cells gone from atrophy.
Some cases in which you see an isolated small acinus
cannot be resolved and should probably be called "atypical small acinar proliferation
suspicious for malignancy". This is NEVER a final diagnosis, but means, "We can't definitively
say that the biopsy shows cancer." (There was maybe only one or two glands.
It could be sclerosing adenosis. It could be
high-grade PIN. It was really tiny and we think it's atrophy but we can't rule
out the "atrophic" version of prostate cancer.
It could inflammation with reactive change. Biopsy can produce
artifact especially along the edges. We made a deeper cut to do immunochemistry and
the little lesion was gone. Basal layer was gone but the cells looked benign. And so forth.)
Nowadays, this diagnosis is followed, more often
than not, by frank cancer (Arch. Path. Lab. Med. 130: 952, 2006 by Dave Bostwick;
also Am. J. Clin. Path. 128: 648, 2007).
Update on "current prostate biopsy interpretation": Arch. Path. Lab. Med.
130: 835, 2006; the immunostains Am. J. Clin. Path. 123: 231, 2005;
combining three Am. J. Clin. Path. 127: 248, 2007.
* On fine needle aspiration biopsy, pathologists pay special attention
to the presence or absence of the basal layer, which conveniently will
lie in its own plane of focus.
I: Glands with some stroma between, sharp edge to the lesion (rare, you'll probably not diagnose it except as an incidental finding on prostatectomy)
II: Glands that are very crowded, less sharp edge to the lesion
III: Nests / cribriform pattern / tiny glands
IV: You can still tell it's of glandular origin, but the acini are very abnormal or fused
V: You can't really tell it's of glandular origin OR you see masses of necrosis
* Gleason grading is not precise and there is considerable
inter-pathologist variability: Arch. Path. Lab. Med. 129:
1004, 2005. More generally, prostate pathology is
difficult. One group in Japan recommends review of all radical prostatectomies
for grade and margins by sub-sub-specialists (J. Urol. 183: 952, 2010.)
Grade correlates with stage and prognosis. Most prostate cancers, even the ones that have
metastasized, are fairly well-differentiated adenocarcinomas.
*
Biomarkers (microarray technology -- i.e., which genes are activated?):
Nature 412: 822, 2001; Cancer 104: 209, 2005.
Genetics update, especially about signature translocations plus androgen-dependence and its loss:
Arch. Path. Lab. Med. 133: 1033, 2009.
* One surprise (from Walter Reed) is that if there is a single focus
of cancer in a prostatectomy specimen, the prognosis is worse than if there
are several foci, all other things being equal. Think why that might be
(J. Urol. 182: 2689, 2009).
* Staging of course also affects prognosis.
For the TNM system --
Tx: occult tumor
T1: not palpable, within prostate
T2: palpable, within prostate
T3: through the capsule
T4: fixed or invades something other than the seminal vesicles
Nx: nodes not assessed
N0: no nodes
N1: one positive node, 2 cm or less
N2: no node 5 cm or larger
N3: some node 5 cm or larger
Mx: metastases not assessed
M0: no distant metastases
M1: distant metastases
More familiar:
A1: well-differentiated carcinoma on 5 or fewer turp chips / fewer than 3 foci / fewer than 5% of the
chip mass (rules vary).
A2: still occult, but on more than 5 chips or high-grade
B: palpable nodule
C: through the "capsule" or in the seminal vesicles
D: metastases
Before you decide you can tell benign from malignant
reliably on physical exam, note that even a pathologist
with the sectioned gland in his/her hand prior to microscopy is only 2/3 sensitive
and 5/6 specific (Am. J. Clin. Path. 110: 38, 1998).
Uncommon prostate cancers include squamous and large-duct (the former "endometrioid"),
plus adenoid-cystic, colloid, carcinosarcoma, signet-ring,
oat-cell, carcinoid, and lymphoepithelioma.
All but the most anaplastic express PSA.
Cancer of the prostate seldom causes problems (or is diagnosed) unless it spreads.
Rectal exam is still the most effective method of diagnosis (cost per life saved a mere $6300; see
JAMA 252: 3261, 1984).
For more on "prostate specific antigen", see the upcoming lecture on cancer screening and
monitoring. Nowadays, urologists are likely to do sextant biopsies on prostates of
men with elevated PSA's and no palpable lump.
Prostate cancer is often indolent even when it has metastasized, but some prostate cancers are very
aggressive.
* Mucin-producing prostate cancer is an aggressive lesion with its own
molecular signature; it is probably a different disease (J. Urol. 54:
141, 1999).
* Finasteride has been offered for prostate cancer prophylaxis (NEJM 349:
205, 2003). On the plus
side, there was a few percent fewer cases of low-grade prostate cancer.
On the minus side, there was no change in the rate of high-grade prostate
cancers or cancer deaths. You'll have to decide for yourself whether the effects
of taking finasteride at these doses (fewer and softer erections, diminished
seminal fluid volume, loss of chest hair, preservation of scalp hair) are good or bad.
You will care for many patients with metastatic prostate cancer.
Prostate cancer typically metastasizes to the axial skeleton (there's a direct connection
between the prostate and the valveless venous plexus that surrounds the inside of the spinal column), eventually causing miserable bone pain.
(Future radiologists: prostatic metastases are often osteoblastic.)
Prostate cancer seldom producers actual brain metastases, but is also infamous
for metastasizing to the leptomeninges.
{17012} prostate cancer in bone, x-ray
Serum acid phosphatase (* tartrate inhibited) is a classic tumor marker for prostate cancer (see
JAMA 253: 665, 1985). The best new tests measure only the prostatic component.
Patterns of metastatic spread: Cancer 54: 3078, 1984.
Treating prostate cancer:
Surgery and/or radiation are useful for localized disease. Conventional chemotherapy is of limited
usefulness in prostate cancer, but protocols do exist.
Prostate cancer is usually quite responsive to endocrine manipulations.
Castration (orchiectomy -- still works well for patients willing to undergo it) and/or estrogen therapy (causes cardiovascular problems) were
for many years the standard treatments for patients with symptomatic bony metastases. Now they
are being replaced with newer agents.
One important new agent is leuprolide, a GnRH (gonadotropin releasing hormone) agonist.
* When large amounts of leuprolide are present for a while, the pituitary stops making GnRH
receptors and thus stops making gonadotropins. (Seems paradoxical, doesn't it?) The patient soon
has stopped making androgens, and the prostate cancer cells undergo apoptosis.
* The histopathology of leuprolide response is sufficiently distinctive to be recognizable by a good
pathologist: Cancer 73: 1472, 1994.
Another approach is the non-steroidal anti-androgen Flutamide, which shrinks prostate cancer
supposedly "without causing impotence".
The anti-fungal agent ketoconazole blocks synthesis of androgens and has also proved useful as an
anti-prostatic cancer drug.
* Future oncologists: Etidronate treatment for refractory bone pain -- it seems to work
by preventing formation of new bone.
With the focus on early detection, it's worth remembering that low-grade, low-stage prostate cancer,
treated very conservatively, doesn't seem to shorten life expectancy (JAMA 274: 626, 1995).
Nowadays, of course, you can follow the course of treated prostate cancer with serum prostate
specific antigen, the same stuff as you use for screening: Mayo Clin. Proc. 69: 69, 1994.
To date, no one has produced any "evidence-based" support for any of a host
of "alternative and complementary" remedies for prostate cancer (Urol. Clin. N.A. 33: 237, 2006).
LOOKING AT PROSTATE BIOPSIES:
A FEW ADDITIONAL IDEAS:
There is no difference between a wise man and a fool when they fall in love.
Despite "conventional wisdom", impotence is often organic, even in younger men without obvious
disease. Ask the guy if he gets erections out of bed, or try the famous low-tech "postage-stamp coil"
test.
In Portugal, not known for being wild, the doctors have developed a
"visual erotic stimulation test" that they concluded
will give an erection to any guy
not organically impotent (J. Urol. 157: 134, 1997).
Even tiny prolactinomas are notorious anti-aphrodisiacs. See JAMA 249: 1736, 1983.
Injection therapy (phentolamine, prostaglandin E1, papaverine) for the guy to use when he wants an
erection: Arch. Phys. Med. Rehab. 75: 276, 1994. Viagra: Too many articles to count,
all in 1998.
Watch for cabergoline therapy (anti-prolactin) to increase male libido.
Blunt trauma to the shaft during masturbation or
intercourse can crack the side of the dorsal vein, allowing blood to drain in easily and causing
impotence. How to fix it: J. Urol. 148: 1171, 1992.
Update on injuries during romance: J. Trauma 62: 1522, 2007.
For premature ejaculation, if the guy doesn't get good results from the squeeze technique (which is
fun), try a selective serotonin reuptake inhibitor (Am. J. Psych. 151: 1377, 1994; dudes: these'll improve an
anal-retentive outlook on life, too). Some men cannot ejaculate; for the electronic gadget that helps,
see J. Urol. 152: 1034, 1994. Retrograde ejaculation results from failure of one of those little bands
of muscle to relax; ask about whether he's taking thioridazine, or an anatomic cause (J. Urol. 151: 1017, 1994).
Viscerosomatic reflex: Very rapid overfilling of the prostate and seminal vesicles (i.e., prolonged
arousal without ejaculation in a young male) results in pain referred to the testes that can be
severe ("blue balls", "lovers' nuts", etc.) The cure is ejaculation by any means. Your instructor
suspects the mechanism is pressure of the seminal vesicles on the genitofemoral nerves.
Junk science! Hey dudes, are we being un-masculinized by rampant estrogen pollution (diethylstilbestrol cattle-fattener, women's oral
contraceptive pill components excreted unchanged, other substances)? In a
widely-publicized paper, researchers presented evidence that the average sperm count has declined
by half over the 1900's (Lancet 341: 1392, 1993, totally unconvincing graph Science 265: 308,
1994). This was based on a handful of determinations of "average sperm counts"
from before 1970 compared to today. There has been no drop since 1970.
There is exactly no evidence that male infertility is increasing: NEJM 332: 327, 1995. So
far there's a single claim, from Finland (Br. Med. J. 314: 13, 1997) that testicular histology has
changed. (Anybody noticed a decrease in testicular size? I don't think so....) The most recent studies
have failed to show an effect, or shown the counts to be increasing with time, or shown how
inaccurate sperm-counting must be (i.e., New Yorkers counted in the New York lab averaged
exactly twice the counts for Angelinos counted in the L.A. lab; Br. Med. J. 312: 1183, 1996). And
if un-masculinization were really at work, your lecturer believes we modern men would have less
body hair, less baldness, less B.O., and less belligerence. Nuh-uh! Your lecturer thinks
that
modern-day dudes simply ejaculate more often (you can figure out why yourself,
and this has been confirmed in interviews) and
resorb less fluid between ejaculations, concentrating the sperms less. Alternatively, today's man
stays excited longer beforehand, producing more fluid. Every teenaged guy knows about this stuff,
but the authors of the original paper apparently didn't think of this; I called them on it immediately,
and the NEJM article above thought that "duration of abstinence" was probably the explanation too.
Since this paper, there has been a silly media hype,
and an inflammatory best-seller ("Our Stolen Future").
A Greenpeace poster of a man with a tiny penis
proclaiming "You're not half the man your father was"
(the campaign is over and the claim has disappeared from the Greenpeace
website, no "sorry about the mistake / sorry we lied" though -- 2008).
There was an even sillier discussion on the floor of the U.S.
senate. The most obvious source of substantial xeno-estrogen exposure
is soybeans. Have you heard of any "socially-conscious
environmentalists" calling
for a ban on tofu? Of course not.
* Some men have had accidents. See J. Emerg. Med. 8: 305, 1990 (caught in the zipper), Acta.
Urol. Jap. 34: 514, 1988 abstract 88267069 (caught in a milk bottle for seventeen hours),
J. Urol. 170: 2385, 2003 (hard-to-cut plastic bottle finally yields to a
stryker cast saw);
J. Urol.
147: 1265, 1992 (all about bites, come in early if it happens to you, dude, 'cause infections can be
really bad), J. Urol. 133: 1046, 1985 (etiology of "sclerosing lipogranuloma", you would enjoy
reading this one),
guy electrocutes himself while attaching the second electrode to his penis
(the first was in back -- AJFMP 19: 198, 1998);
Plast. Rec. Surg. 91: 352, 1993 (review of sclerosing granuloma, with a case
study of a guy who injected himself with transmission oil in the hopes of having a permanent
erection; bad idea, fellow); J. Urol. 134: 274, 1985 & Br. J. Surg. 89:
555, 2002 (fractures of the erect penis),
J. Trauma 56: 1138, 2004 (by far the most common cause of fracture is striking
the female pubic bone too forcefully);
Urology 24: 18, 1984 (rings), Plast.
Rec. Surg. 87: 771, 1991 (electrical injury), J. Emerg. Med. 8: 419, 1990 (young skateboarder
impales scrotum on a metal rod), Br. Med. J. 281: 26, 1980; Br. Med. J. 281: 591, 1980; JAMA
224: 630, 1973; Urology 25: 41, 1985 & Indiana Med. 81: 252, 1988 (vacuum cleaners; there are
several other articles on the same subject), Urology 26: 12, 1985 (foreign bodies), Urology 26: 50,
1985 (pet rattlesnake), J. Urol. 153: 1929, 1995 (alligator, reconstructed after 20 years and it worked),
Br. J. Urology 74: 121, 1994 (pig),
Plast. Recon. Surg. 108: 805, 2001 (another pig),
Urology 26: 81, 1985 (necklace), Am. J. For. Med. Path. 7: 254, 1986 ("Eddie Spaghetti"), Genit.
Med. 68: 334, 1992 (penicillin bottle under an enormous foreskin), electric cable, paper clip,
tweezers, etc., (Br. J. Urol. 68: 510, 1991),
J. Roy. Soc. Med. 98: 122, 2005 (magnet and metal);
Arch. Sex. Behav. 34: 469, 2005 (bottles);
Int. Ur. Neph. 25: 77, 1993 (uses high-tech term "SFB"
for self-inserted foreign body), guy self-injecting olive oil into his scrotum to make it bigger gets fat
embolus (Chest 107: 875, 1995), romantic love between a man and his hydraulic tractor ends in
death (J. For. Sci. 38: 359, 1993), Med. Asp. Hum. Sex. July 1991 (guy in love with a sander belt
loses a testis and repairs himself on-the-job with his handy staple gun; much-photocopied).
Two guys mutilate their genitals elaborately while high on amphetamines (Addiction 97:
1215, 2002); both said it was extremely pleasurable at the time and both
continued the drug use and the self-mutilation. There's no figuring drug-users out.
Huge review of gunshot wounds: J. Trauma 64: 1038, 2008.
"Alcock
syndrome" is insensitivity of the penis (lasting up to several weeks) resulting from pressure on the
pudendal nerve (which runs through "Alcock's canal") during bicycling. Mishap with the
laser: Urology 48: 155, 1996. Caught in the zipper? See Injury
25: 59, 1994 -- easy to manage.
Complications of
penis-piercing, now become popular in the US: Cutis 60:
237, 1997.
A "cultural practice" in
some Asian communities is attempting suicide by cutting off the penis
and bleeding to death (Am. J.
Psych. 150: 350, 1993). Even less amusing: In past wars, when a captured man was being tortured either
for information or fun, mutilating the genitals was commonplace. This was fairly common as
recently as the Vietnam era (both sides), and surfaced again in Bosnia. Stay tuned for the war-crimes trials.
Sexual torture:
Lancet 345: 1307, 1995. Injury to the vas deferens from torture: Br.
J. Urol. 72: 515, 1993.
In "the new South Africa", the phenomenon of "Muti killing" has emerged
in which body parts are excised from victims while they are still
alive in the belief that these can be used to cure diseases
such as AIDS (Med. Sci. Law 46: 255, 2006); boys are likely to
have the genitals cut off.
Sexual abuse of a child in any form is one of the vilest and most disgusting
things a person
can do.
We hear mostly about fondling (which does no physical damage but
is supposed to lead
to terrible lifelong emotional scarring).
The GAO's 1996 review of whether children who get molested go on to
become child molesters themselves and documented the difficulty of studying
this scientifically -- the prospective studies would lead most readers
to conclude that it really doesn't.
However, boys who are abused sexually
often have severe physical damage in addition / instead (burns, cuts, crush injuries;
Arch. Dis. Child. 92:
328, 2007 acknowledges that nobody's paid attention -- the politics is so bizarre).
Reconstructing a youngster's penis using microsurgery, so that it works: J.
Urol. 149: 1521, 1993. A grown-up's amputated penis is re-attached and still works: J. Urol. 147:
1628, 1992. Another Arch. Sex. Behav. 19: 343, 1990. We await publication of the full details of
John Wayne B....
A penis that, when stretched to its maximum flaccid length (which is pretty much the same as its
fully-erect length), is shorter than 2 SD below the mean for the guy's age is an official
"micropenis". For a grown man:
11 cm: 10th percentile
13 cm:
50th percentile
15 cm:
90th percentile.
Lots of guys have some curvature, most often upwards, often downwards,
sometimes a little to one side or the other (J. Sex. Marit. Ther. 23: 195, 1997).
Among a group of men 4-10 cm, the consensus was, indeed, that "it's not what you've got, it's what
you do with it." (Not stated in exactly these terms, of course, and partners were not surveyed by the
tactful researchers; see J. Urol. 142: 569, 1989). The cause is probably androgenic deprivation for
some reason during embryogenesis (Arch. Dis. Child. 66: 1033, 1991).
* Agenesis of the penis: J. Urol. 143: 338, 1990. Two of them (diphallus): J. Urol. 142: 356, 1989.
* Your lecturer predicts male circumcision will remain popular for newborns,
as well as a popular choice for older males.
It has long been politically incorrect
for pediatricians to recommend routine circumcision of newborns,
despite the obvious health benefits for some gruops.
In 1999,
the American Academy of Pediatrics issued a new statement affirming that
there are real health benefits, but not enough to make the right
choice obvious, and of course asking
that an anesthetic be used (Pediatrics 103: 686, 1999).
Circumcision in infancy
prevents cancer of the penis quite effectively, and it greatly (10 x, from 1 in 100 to 1 in 1000;
not "slightly",
as the AAP states) reduces urinary tract infections
in little boys (Pediatrics 83: 1011, 1989; good review, everything I've
seen since this
confirms this; most recent Lancet 352: 1813, 1998). Hygiene is much easier, the risk of catching
AIDS from a woman during normal lovemaking is much less (NEJM 319: 274, 1988,
Nat. Rev. Micro. 3: 914, 2005;
Urol. Clin. N.A. 22: 57, 1995, Sci. Am. 1996;
Lancet 369: 643, 2007;
Lancet 363: 1039, 2004 shows the risk is cut
by 5/6, though there's no comparable benefit for syphilis or gonorrhea),
the other common sexually transmitted
diseases are harder for him to catch (NEJM 322: 1308 & 1312, 1996;
STD's in general Pediatrics 118: 1917, 2006 -- curiously, no "political incorrectness" disclaimer;
HPV Lancet 369: 657, 2007; Br. Med. J. 334: 712, 2007;
prevents herpes 2, HPV and HIV but not syphilis NEJM 360: 1298, 2009;
dissenting prospective study J. Ped. 152: 383, 2008), and what's more, many
people like it ("Mine looks streamlined, it's my pocket-rocket, yours looks dirty;" most women
prefer for that special man to be circumcised: Pediatrics 105: 620, 2000). An
uncircumcised man's glans is a bit more sensitive (i.e., more intense sensations, both pleasant and
unpleasant? less total time before ejaculation?; men who've been circumcised as adults have told me
about both).
In order to appease anti-circumcision militants, the AAP
included only the unsubstantiated claim that circumcision reduces the man's pleasure
in its "Information for Parents." Of course the media spun the whole
position statement as "Circumcision is no longer recommended."
Opposition to circumcision deals with other issues
than physical health.
Opponents cite "unnatural", "a male's right to make the decisions affecting his own
body", "religious freedom", "problems of the uncircumcised are treatable" (except HIV and
gangrene, of course; the latter can happen to an unwashed little boy).
Sexuality is powerful, individual, and incomprehensible.
The truth is that any boy has a fair chance of growing up to be a man who
really likes having a foreskin and/or bitterly resents not having one.
And the latter's a real problem, much worse than having a few kidney scars
from an infection.
Right now there's considerable
anti-circumcision activism among men across the Kinsey scale ("I will NEVER forgive my
parents for..."), though this is based on personal-freedom issues
rather than health issues.
Since we're comparing physical health and emotional satisfaction,
the right choice will never be "clear-cut" (ha ha).
The medical literature is starting to break politick silence about
a terrible problem in the poor nations -- "traditional healers" who perform
circumcisions as a result
of which "not uncommonly, amputation occurs" (Ann.
Plast. Surg. 44: 311, 2000).
South Africa prosecutes one of these quacks for murder (Br. Med. J. 313:
647, 1996 -- "the [tribal] king complained that gross damage was being
done [by the prosecution] to a culture that was the pride of the nation.
His complaint was not upheld.").
Things do not seem to be improving in "The New South Africa": Curationis 27:
57, 2004; the "traditional society" is obviously subjecting the boys
to willful, cruel abuse -- continuing problem Soc. Sci. Med. 70: 729, 2010 (even
this far-left ultra-multiculturalist journal knows its wrong).
The mohel may kiss the circumcision site and transmit
herpes * Men with endometriosis (I always believed in the coelomic metaplasia theory rather than the
reverse menstruation theory, anyway): Eur. J. Surg. 158: 7, 1992; Am. J. Ob. Gyn. 165: 214, 1991,
others.
* When men of my generation get old, we men will probably get hormone replacement, just as many
women do. This is probably a good idea (NEJM 334: 707, 1996; Br. Med. J. 312: 859, 1996;
Ann. NY Acad. Sci. 774: 128, 1995; update NEJM 350: 482, 2004)
DHEA (the miracle-claims "nutritional supplement" of 1997) flunks
tests of its ability to produce psychological benefits: J. Clin. End.
Metab. 82: 2363, 1997. No one knows how many men get hypogonadism
as they get older, or what is physiological; many, probably most, men do not
undergo "andropause" (BMJ 337: b352, 2009). Stay tuned on this.
The British found no link between vasectomy and testicular cancer, prostate cancer, or any other of
the common diseases for which they sought a connection: Br. Med. J. 304: 743, 1992. Surprised?
Of course not. Full of disclaimers about insufficient duration, insufficient patient numbers, etc.
* Among adults, only ideologues won't recognize that sexual behavior (broadly
defined) has many purposes (good, bad, indifferent) in addition to fertilization. As far as I know, all
durable societies have decided that a stable, lifelong, committed, faithful relationship is
by far the best
setting for sex. (Margaret Mead was, of course,
the victim of a hoax by some teenagers.)
It is one thing to be compassionate; it is quite another to advocate
attitudes and behaviors that will predictably lead people
to harm themselves and others. (I see this as a problem today in the U.S.;
you might disagree.)
People think about sex a lot, and we know that making it a
taboo subject or a big dreadful mystery is asking for trouble, just as having
casual sex is always asking for trouble. The wise adult learns that setting
limits is the key, and decides what limits to set. Not everyone does this. Further, it is easier (and
better power-politics) to get up on a soap-box about sex than to try to understand it. As a physician
you must at least do the latter. Male sexuality becomes a major concern for the pathologist when it
leads to death (i.e., homicide, in which sex is usually a factor, suicide, in which sex is often a factor,
and autoerotic asphyxia, which is not rare) or when it involves someone who does not, or cannot,
consent. Almost every man realizes that to force himself on another person (employee, family
member, date, stranger, child) is shameful, wrong, disgusting, and un-masculine. Most men also feel
entitled to "get their loving", and for many men, self-esteem gets tied up with "getting it". Most
bright men figure out early that self-control, though difficult, is muy macho. For some men,
controlling the urge to act-out sexually (which can take various forms, some of them harmful for
other people) is as hard as sticking to a weight-reduction diet (see especially Psych. Clin. N.A. 15:
675, 1992). Probably these men have a wiring problem, whatever else may have gone wrong, and a
psychiatrist can help (swallow your pride, dude; major review Psych. Clin. N.A. 15: 703, 1992;
clomipramine fixes up a compulsive flasher Am. J. Psych. 149: 843, 1992; fluoxetine cures a
Peeping Tom: Am. J. Psych. 148: 950, 1991; naltrexone (the opioid
antagonist popular for alcoholics, drug abusers, compulsive eaters,
obsessive-compulsives, and impulse-control problems)
now finds its use for sexual acting-out as well (J. Clin. Psych. 65:
982, 2004).
there's behavioral, insight, and pharmacological ways
of helping most problem guys, if they want to be helped, and for criminal-justice cases, there's now
leuprolide, which works better than saltpeter). Perhaps the most interesting article on male sexuality that
your lecturer has ever seen was a prison survey in which 23% of prisoners admitted to having been
forcibly raped by a male bully, and those who could tell the interviewer about this without becoming
visibly and acutely upset were almost all sex offenders. The conclusion is that at least a good
number of sex offenders come to terms with what's happened to them by acting out "in a strange and
cruel way" (Med. and Law 12: 181, 1993). There's gotta be a better way of making sense of what's
happened to you; perhaps a family physician, talking sense and explaining "you're still a man", etc.,
etc. could have made all the difference. Your lecturer finds a Don Juan as baffling as a gourmet,
and a man with a pornography obsession as puzzling as the "Food" section of the Kansas City Star.
So do the vast majority of men, who are bored by and ridicule tasteless displays of sexuality.
This is the truth.
It is also very hard for a man to defend against a false accusation of rape (in spite of what you've
been told by "women's advocates", this is all-too-common; ask a cop
(how the British police decide: Medicine Science & the Law 36: 135, 1996), or stay tuned for the next few
lectures), and the forensic pathologist can make all the difference here. A study at Purdue showed
to my satisfaction that at least 40% of accusations are false (Arch. Sex. Behav. 23: 81, 1994) -- women
seeking revenge or attention. With over 200 convicted men now exonerated by DNA evidence,
this should prompt serious thinking before anyone is convicted solely on someone's word.
The US Air Force, which is reality-based,
discovered that at least 60% of women crying "Rape!" were lying --
indeed, many confessed.
(Forensic Science Digest 11(4): 64, December 1985).
Today, even the conservative Victoria Forensic Science Center considers
"false sexual assault" to be a common diagnosis that the physician can make
just by examining the clothing (J. For. Sci. 45: 568, 2000).
If you are accused of rape or
child molestation, dude, you can now have your penis hooked up to a pressure sensor, get read dirty
stories and shown dirty pictures, and your erectile responses used as evidence against you in a court
of law ("phallometry"). During the height of "political
correctness", these studies were done with a total
lack of control, and an obvious
misandrism: J. Con. Clin. Psych. 58: 886, 1990; Arch. Sex. Behav. 20: 75,
1991. I think most people know that
lots of things are turn-ons for lots of dudes, even us well-behaved ones: demonstrated Arch. Sex. Behav. 20:
137, 1991. When researchers started applying controls to phallometry,
it became clear (as I predicted)
that whether a guy gets excited by seeing various
anti-social acts has very little
correlation with what he'd actually do / has done (Arch. Sex. Behav. 23: 295, 1994).
I envision a control group composed
of people who have made political capital (right-wing, left-wing)
by accusing others
of sexual misconduct.
Neither gender has a monopoly on good and
evil, but currently the law places men at certain
disadvantages that puzzle me.
For example, a woman's previous false accusations of rape, even
if numerous, cannot be mentioned by a man in his own defense.
If a man passes a polygraph exam, and there is no physical
evidence against him, and he appears utterly sincere,
and it's simply her word against his, the man gets
told that he is a rapist and is "in denial".
If the physical evidence contradicts the accuser's story,
the "child protection
advocates" will egregiously misuse the scientific literature (notably
Pediatrics 94: 310, 1996).
You can cite additional examples.
One way to protect yourself is obtain specific and verbal permission prior to each step of the
lovemaking process (that's gentlemanly and fun).
Speaking of "links", in the one massive study comparing normal men, rapists, and child
molesters, "frequency of adult use of sexually explicit material does not differ significantly among
groups".
Nor did the frequency of sex crimes increase in Sweden when they made the even the most
dopiest-nastiest stuff as available as alcohol and tobacco. See J. Sex. Marit. Ther. 19: 77, 1993.
I'd like an easy scapegoat, too, Mr. Bundy, but the roots of your evil
went much, much deeper. The pop claim is that x-rated stuff is naturally
addictive (like tobacco or heroin) and leads to escalating tensions
that must eventually be acted out. This may be true for individuals
like the young Mr. Bundy,
and probably specialist treatment would be wise sooner rather than
later. It's clearly not true for the vast majority of men, or the
world would be a far different place. But we're into politics rather than science.
And as politicians and "progressive thinkers" tell us over and over about
the dangers of erotica, I still hear almost no complaints about the
vile school of rap music with lyrics that degrade women and glorify sexual violence.
The evidence that this causes to violence against young women
in the underclass communities is impressive (Pediatrics 118: e430, 2006).
Go figure.
The
paraphilias: Psych. Clin. N.A. 15: 675, 1992. "A review of sexual behavior in the United States":
Am. J. Psych. 151: 330, 1994.
Natural selection obviously is much harsher on men than on women, and this
is the case throughout nature. Is this why there's sex? Nature 411:
689 & 692, 2001.
* "Solitary vice." One of the silliest health claims, which persisted from ancient times up until the middle
of the 20th century, was that masturbation (male, female) was a major risk factor for everything.
History of the "superstition" (is this the right word?): West. J. Med. 175:
66, 2001. Both Graham crackers (invented by an ultraconservative Protestant pastor)
and Kellogg's cereals (invented by a quack physician) were introduced to help
young people refrain from this "heinous practice."
Pathologists and serious clinicians never believed this nonsense,
and it was primarily a political-"spiritual"
thing. It would be
difficult to find a control group. See Am. J. Psychoth. 45: 9, 1991;
Arch. Neurol. 51: 600, 1994.
Some of the authoritarian
sects still talk about masturbation as a sin
for which you will go to hell.
I have noticed that these are the same sects that tell teenagers
that they should get married early
and have big families; you'll need to decide for yourself.
Someone more cynical than I am could see even darker motives -- the
cultivation of fear and even of hypocrisy as a way of life.
Many teenaged boys suffer terrible conflicts over
this.
There have been some highly-publicized suicides.
Occasionally
teens E-mail me about "overcoming this problem"; when I was a college
student, a classmate told me he was considering suicide over
his inability not to masturbate (I got him together with a
sensible pastor of his denomination and this helped.) As a doctor, you'll
need to be aware of this issue, which Junior might not bring up --
and you might not even think of it. Among adults, certain self-help groups
focused on helping people stop habits of sexual acting-out that
hurt themselves and others. Some of these groups try to keep clients
from masturbating as part of a program of "sexual sobriety".
Sub-science -- personal impressions acquiring the status
of dogma -- strikes again. And of course this "program"
didn't help the behavior
problems after all (Arch. Sex. Behav. 25: 397, 1996.)
The bizarre subterfuges to which some men go to avoid "sin" and still masturbate:
J. Sex. Marit. 24: 37, 1998.
As a physician, no matter
what your religious background, it seems to me that you have
a duty to protect young people's mental health and lives. This area is
extremely delicate and difficult.
* Heard that FSH is necessary for Sertoli cell development, spermatogenesis and fertility? Surprise -- it's not (though it
helps; in mice or men, Nature Genetics 15: 201 & 205, 1997).
Potiphar's Wife, by Rembrandt
* SLICE OF LIFE REVIEW
{00083} testes, normal
When I was one-and-twenty
-- A.E. Housman, "A Shropshire Lad" Now I am two-and-twenty,
Samuel Hoffenstein,
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.
Bristol 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
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
PathologyPics -- where pathologists share favorite images. Thanks!
WebPath:
Internet Pathology
Laboratory -- great site
My team:Ed Lulo's Pathology Gallery
Also:
Bryan Lee's Pathology Museum
Dino Laporte: Pathology Museum
Tom Demark: Pathology Museum
Path Consult -- great photos and text for more advanced learners
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
LEARNING OBJECTIVES
Describe the following anatomic defects, how they arise, and what may
happen as a result:
Epispadias
Phimosis
Paraphimosis
Peyronie's
Pearly papules
Hydrocele
Varicocele
Spermatocele
-- St. Augustine, Confessions
-- Socrates
Iron John. Iron John. What MY wife wants
is iron-ING John!. -- Anonymous man
{10268} prostate, normal gross section
{11762} prostate, normal histology
{11763} prostate, normal histology
{17008} prostate, normal histology
{15027} prostate, normal histology, with concretion
{00083} testis, normal histology
{20941} testis, normal histology, good Leydig cell
{15016} epididymis, normal histology, with sperms
{15026} seminal vesicles, normal histology
{25832} sperms, Pap stain; note two-headed sperm in center (not too unusual)
Testis, epididymis, penis
"Pathology Outlines"
Nat Pernick MD
-- Hillel
While you are away, movie stars are taking your women. Robert Redford is dating your girlfriend.
Tom Selleck is kissing your lady. Bart Simpson is making love to your wife.
loosener of limbs, by whom all gods and all men
find their thoughts and wise counsels overcome in their hearts.--Hesiod
Lower Urinary / Male
Taiwanese pathology site
Good place to go to practice
Urologic Path
Surgical Pathology Atlas
Nice photos, hard-core
Reproductive
Surgical Pathology Atlas
Nice photos, hard-core
Reproductive
Utah cases for path students
Juliana Szakacs MD
Penis Exhibit
Virtual Pathology Museum
University of Connecticut
To date, no gene has been identified that causes what must be a multifactorial-etiology
problem. Not surprisingly, the first statistical link is to the 5-alpha-reductase
gene (J. Clin. Endo. Metab. 90: 6695, 2005), which activates testosterone
on the skin and is inhibited by today's baldness-cures.
Congenital phimosis
Wikimedia Commons
* Jogger's phimosis: Br. J. Ur. 63: 549,
1989.
The word "phimosis" can also be used when scar contraction causes narrowing
following circumcision in the newborn (J. Urol. 169: 2332, 2003)
or balanitis xerotica in a kid (J. Urol. 165: 219, 2001 -- this is a lichen
sclerosus variant, usually seen in uncircumcised males and which is
helped by circumcision: South. Med. J. 96: 7, 2003).
,
mycoplasma, others), are important sexually-transmitted diseases.
Gonorrhea tends to come on fast after the contact, while
chlamydia
comes
on insidiously. Gonorrhea tends to have a more purulent
discharge.
,
and there is now substantial support for the idea that chlamydia
do indeed infest the
synovium (Arth. Rheum. 35: 521, 1992 was the first paper).
If the initial episode of urethritis is treated appropriately,
reactive arthritis's is much less likely to ensue (Arth. Rheum. 35: 190, 1992).
Gonorrhea may also produce reactive arthritis.
Warts
Male patient photos
Health Awareness Connection
. Typically occur in skin folds.
is familiar to you.
Pearly penile papules
Patient photo
From a correspondent -- thanks
Pearly penile papules
And other adolescent skin stuff
USC Keck
Pearly penile papules
Classic look
Wikimedia Commons
{46451} squamous cancer of the penis, with inguinal node metastasis
Cancer of the Penis
Dino Laporte's PathosWeb
Three diseases, all usually occurring in uncircumcised men.
{25096} erythroplasia of Queyrat, histology
{25102} verrucous carcinoma, histology
-- Elbridge Gerry, Constitutional Convention 1787
-- Lyndon
Baines Johnson
-- Charles Colson (pre-conversion), about the Vietnamese
Testis Exhibit
Virtual Pathology Museum
University of Connecticut
,
cryptorchidism, some cases of old age, after radiation, after some kinds of
chemotherapy -- all will give a "Sertoli-only" histology) and unknown.
{25154} testicular feminization (no sperms, hyperplasia of useless Leydig cells, why?)
Epididymis Exhibit
Virtual Pathology Museum
University of Connecticut
:
orchitis is common in adolescents and adults. It usually follows the onset of parotitis by a
week or so, and may cause atrophy of the germinal epithelium and infertility. The Leydig cells are
spared.
* Thanks to anti-immunization activism, there has been a tremendous
resurgence in Europe. See J. Roy. Soc. Med. 99: 573, 2006.
: granulomas involving the epididymis; may spread to the testis.
* BCG epididymitis
and orchitis: J. Urol. 148: 1534, 1992.
: gummas involving the testis; may spread to the epididymis.
{25208} torsion, gross
{10898} testes: normal vs. "atrophic" (could have been old torsion, old mumps, or whatever)
Torsion
WebPath Photo
Fournier's gangrene
Synergistic gangrene
Photo from surgical-tutor.org.uk
Fournier's gangrene
Synergistic gangrene
From a Vietnamese site
GERM CELL TUMORS (cancer of the testis): Cancer of the germinal epithelium. These tumors
are the commonest solid cancers of men in their 20's and 30's.
In 2006, there were around 8250 cses and 370 deaths in the US.
Pathologists see Arch. Path. Lab. Med. 131: 1267, 2007; J. Clin. Path. 61: 20, 2008.
Clinicians see Lancet 367: 754, 2006.
* The 2004 World Health Organization classification seems to be standard now.
This isn't something that beginning pathology learners need to see,
especially as WHO classifications are under continual revision. (Curiously,
one of the things that the United Nations does well is pathology.)
Remarkably little is known of the molecular biology,
despite their importance. The best-known finding is that the tumors
of young adults (but not the pediatric tumors or spermatocytic
seminoma) usually feature amplification with an isochromosome of the
short arm of 12.
The tubules are full of cells with big dark nuclei, big nucleoli,
and abundant, usually glycgen-rich / PAS-positive cytoplasm (normaltubular epithelium
is PAS-negative).
* A study that "showed" that heavy exercise increases a young
man's risk for testicular cancer by 2.5x
(Am. J. Epid. 151: 78, 2000) suffered from a major flaw.
Despite the authors' confidence that everybody was telling the truth in
a retrospective survey,
it seems to me that men who's just lost a testis will want to play
up what macho-athletes they've been. Thankfully (especially with Lance Armstrong)
this obviously bogus "risk factor" never
made it into the news.
The diagnosis on microscopy is easy.
If help is needed, seminomas are positive for PLAP, c-Kit/CD117,
OKT3/4, and podoplanin/D2-40 (reported as "specific for seminomas"),
but negative for epithelial membrane antigen and (usually, mostly) negative
for cytokeratins.
Pitfall: Some of these are metastases from a "regressed primary" in the testis.
Get these guys' testes ultrasounded (J. Urol. 182: 2303, 2009).
{25352} seminoma, gross
{25353} seminoma, histology
{08863} seminoma, histology
{40217} seminoma, histology (PAS stain for glycogen)
{08862} seminoma in situ in the tubular epithelium
{25355} spermatocytic seminoma, gross
{25173} spermatocytic seminoma, histology
Testicular Seminoma
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery
Lymphadenectomy incision
Supposedly belongs to
comedian Tom Green
* If you don't let me play, I'm going to take my ball and go home.
-- Johnny Kruk, Philadelphia Phillies
On being asked not to return to baseball until
he was fully recovered from seminoma surgery
SPERMATOCYTIC SEMINOMA (Arch. Path. Lab. Med. 133: 1985, 2009)
It is now clear that this is a rare indolent tumor of older men,
distinct from true seminoma, unrelated to cryptorchidism, and without a counterpart
in the ovary.
{23956} embryonal cell carcinoma; cartilage and erectile tissue (subtle)
Embryonal cell carcinoma
WebPath Photo
{25402} teratocarcinoma
* Two rarities that remind us that the testis is about reproduction:In adults, it tends to be a component of an embryonal cell carcinoma.
POLYEMBRYOMA features a mix of embryonal cell carcinoma
and yolk sac tumor with a cavity resembling the amnion,
studded with embryoid bodies (i.e., structures like the early
embryo, with the three germ layers.
{11551} yolk sac cancer, histology
Yolk sac carcinoma
Liver
Pittsburgh Pathology Cases
Yolk sac tumor
WebPath Photo
Mixed germ cell tumor of testis
Great photos
Pittsburgh Pathology Cases
Leydig cell tumor
Pittsburgh Pathology Cases
Hydrocele
WebPath Photo
Prostate Exhibit
Virtual Pathology Museum
University of Connecticut
You remember the normal gross and microscopic anatomy of the prostate gland.
The lobes actually are only distinct in embryos.
{25213} acute prostatitis, histology
{25215} chronic prostatitis, histology
cause some of these infections. See J. Urol. 141: 328 & 332, 1989.)
Trichomonas is another candidate (Am. Fam. Phys. 39: 177, Feb. 1989). Autoimmunity is yet
another: J. Urol. 152: 247, 1994). No longer a taboo subject:
heroic abstinence (no partner, no self-entertainment) makes this problem MUCH
worse (Int. J. Urol. 6: 130, 1999).
(hematogenous spread from the lungs), "idiopathic"
(no TB, no caseation, no clues as to the etiology) or * exotic (J. Urol. 143: 365, 1990). * The
histiocytes may resemble cancer cells.
* Before considering the diagnosis of "stromal sarcoma" of the prostate,
be sure you are not simply dealing with the hyperchromatic stromal cells
that one occasionally sees in a hyperplastic stroma (Arch. Path. Lab. Med. 132: 1729, 2008).
{17007} prostate hyperplasia, gross cut surface
{15382} prostate hyperplasia, gross; both gland and bladder have been opened anteriorly
{18766} prostate hyperplasia, gross
{24445} prostate hyperplasia, gross
{17458} prostate hyperplasia, good median bar
{08856} prostate hyperplasia, histology
{17457} prostate hyperplasia, histology
{17197} prostate hyperplasia, histology
{08857} prostate hyperplasia, histology
Prostatic Hyperplasia with Thick Bladder
Australian Pathology Museum
High-tech gross photos
Benign Prostatic Hyperplasia
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery
PROSTATE CANCER: Adenocarcinoma of the subcapsular glands. All about the pathology:
Cancer 70(S1): 235, 1992; Cancer 71(S3): 906, 1993 (deja vu);
changes after therapy Arch. Path. Lab. Med. 131:
360, 2007; review of the disease Br. Med. J. 308: 780, 1994;
Sci. Am. 279(6): 74, Dec. 1998.
Frank Zappa
* The fact that the increased rate is the result of increased screening
is confirmed by the finding that the US uninsured do not show the increase,
and of course present at higher stage (J. Urol. 181: 579, 2009).
Low grade
PIN1: loss of secretion, piling up of cells ("tufting"),
blue cytoplasm, looks lush
High grade (HGPIN)
PIN2: As PIN1, but with high N/C ratio
Future pathologists beware! Some cribriform growth in the center
of the prostate is normal, there's a benign "adenoid-cystic-like adenoid basal
cell tumor", and there's a benign clear-cell cribriform
hyperplasia.
You remember the same claim about breast cancer in the
1980's; it didn't hold up.
Future pathologists: you
can use keratin 34βE12 ("keratin 903" or "K903"; most popular) or some
other special keratin
stain to see the cytoplasm basal layer; if absent or very discontinuous, think cancer.
Grading of prostate cancer is now performed on the Gleason I-V system, based on low-power H&E
pattern of tumor. It has proved enormously valuable and durable since its introduction
over 40 years ago (J. Urol. 183: 433, 2010; Arch. Path. Lab. Med. 133: 1810, 2009). Oversimplified Gleason's:
In the next few years, we'll have the results of the clinical trials of high-intensity
focused ultrasound for localized disease. The computer-assisted technology is of course
a marvel, and I would not be surprised if this becomes mainstream.
{21031} prostate cancer, gross
{18767} prostate cancer, gross; looks yellowish
{03236} hydroureter in prostate cancer
{08865} well-differentiated prostate cancer
{23979} well-differentiated prostate cancer, Gleason 2
{08866} prostate cancer, cribriform, Gleason 3
{08864} prostate cancer, Gleason 3
{23980} poorly-differentiated prostate cancer, Gleason 4-5
{23975} atrophy of the prostate, as, after removal of androgens
{23969} irradiated prostate; note radiation changes in vessel to right of center
Prostate Carcinoma
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery
* Anthony Sattilaro, an MD who claimed
to be cured of prostate cancer by the "Zen Macrobiotic Diet" (even though he'd
undergone conventional therapy),
authored the very famous books "Recalled by Life"(1982) and
"Living Well Naturally" (1984). He died of his prostate cancer in 1989.
Quacks still claim he was cured and is alive.
You will look and feel smart if you know the following. Leave the final
call to your pathologist.
Benign
Malignant
Low magnification?
Architecture intact
Architecture disrupted
Basal layer?
Present (at least discontinuously) in benign lesions and precancers
Usually absent
Nuclei?
Normal-size
Often big; hyperchromatic in high grades
Nucleoli?
Inconspicuous (prominent in some precancers)
Often big and red
Chromatin pattern?
Normal
Often marginated (i.e., mostly at edge of nucleus)
Secretion?
Pale, not basophilic
Often basophilic
Crystals in the lumens?
Almost never
Sometimes
Cribriform pattern ("swiss cheese")?
Certain areas of normal prostate and certain precancers
Gleason III cancers
Perineural "invasion"?
Almost never
May be present
Invasion?
No
Look for indian files
34βE12
Shows basal cells present
Positive in tumor itself: BenignShows basal cells absent
or at least disrupted
P504S / AMACAR / racemase?
Cytoplasm negative
Cytoplasm often positive
Nuclear p63 stain
Often positive (basal layer)
Usually negative
-- Traditional
More stuff on measurements: J. Urol. 156: 995, 1996 found
that the average erect length was 12.9 cm, lower than Kinsey's
15.5 cm. Lower than 7.5 cm: consider surgical enhancement. The vacuum
pump enlargers haven't been given a controlled study, but there's
one report that they help after Peyronie's disease surgery.
(series
of eight cases from Israel; Pediatrics 114: e259, 2004).
By contrast, in the United States, the circumcision rate for newborns
has actually been increasing in all ethic groups except Native
Americans since 1988; it's around 70% in the Midwest
and Northeast, but less than 30% out West, and the more affluent and educated
the family, the more likely they are to have the son circumcised (J. Urol. 173:
978, 2005), even though third-parties are refusing to pay for it
(Urol. Clin. N.A. 31: 461, 2004; J. Urol. 170: 1533, 2003).
The fact that postnatal circumcision will be required for health reasons in almost
10% of boys, and is much more expensive, is now persuading third-party
payers to change their minds about neonatal circumcision (J. Urol. 175:
1111, 2006).
{09753} scabies
{11550} syphilis
{25537} chancre and gonorrhea both
{12598} lichen planus
{12600} lichen planus
{24988} lichen planus
{14133} herpes simplex
{14238} candida
{23958} epidermoid cyst of the testis
{24988} lichen sclerosus
{12188} lichen sclerosus
{12189} balanitis xerotica
{25049} balanitis xerotica, histology
{25116} Fabry's angiokeratomas
{25196} sperm granuloma after a vasectomy
Primary syphilis
Yutaka Tsutsumi MD
{10268} prostate, normal
{10898} atrophy, testes with normal comparison
{11762} prostate, normal
{11763} prostate, normal
{15000} testis (tunica albuginea), normal
{15001} testis, normal
{15002} seminiferous tubule, normal
{15003} seminiferous tubule, normal
{15004} seminiferous tubule, normal
{15005} seminiferous tubule, normal
{15006} seminiferous tubule, normal
{15007} sertoli cell, normal
{15008} sertoli cell, normal
{15009} interstitial cells leydig, normal
{15010} interstitial cells leydig, normal
{15011} rete testis, normal
{15012} rete testis, normal
{15013} rete testis, normal
{15014} ductuli efferentes, normal
{15015} epididymis, normal
{15016} epididymis with spermatozoa, normal
{15017} epididymis with * spermatozoa, normal
{15018} epididymis with stereocilia, normal
{15019} epididymis with stereocilia, normal
{15020} ductus deferens, normal
{15021} ductus deferens, normal
{15022} ductus deferens, normal
{15023} ductus deferens, normal
{15024} seminal vesicle, normal
{15025} seminal vesicle, normal
{15026} seminal vesicle (secretory epithelium)
{15027} prostate with concretion, normal
{15028} prostate with concretion, normal
{15029} prostate epithelium, normal
{15030} prostate epithelium, normal
{15031} prostate epithelium and concretions, nor
{15032} urethra, normal
{15033} urethra, normal
{15125} prostate
{15127} prostate
{15128} prostate
{15129} prostate
{15304} prostate
{15330} seminal vesicle, normal
{15331} seminal vesicle, normal
{15332} testes, tunica albuginea
{15333} testes, tunica albuginea
{15577} testes, normal unfixed
{15578} testes, normal unfixed
{15579} testes, normal
{15580} testes, normal unfixed
{15587} bladder and prostate, normal unfixed
{15589} prostate, normal
{17008} prostate, normal
{20213} prostate, normal
{20652} leydig cell, testes
{20653} rete testis, normal
{20653} rete testis, normal
{20654} rete testis, normal
{20654} rete testis, normal
{20655} testis, normal
{20656} sertoli cell nucleus, testis
{20657} spermatogonia, testis
{20658} testis, normal
{20659} epididymis, normal
{20660} ductus deferens, normal
* When I was one-and-twenty
I heard a wise man say,
"Give crowns and pounds and guineas
But not your heart away;
Give pearls away and rubies
But keep your fancy free."
But I was one-and-twenty,
No use to talk to me.
I heard him say again,
"The heart out of the bosom
Was never given in vain;
'Tis paid with sighs a-plenty,
And sold for endless rue."
And I am two-and-twenty,
And oh, 'tis true, 'tis true.
* When I was one-and-twenty,
My ills were in their prime,
With aches and pains aplenty,
And gout before my time;
I had the pyorrhea,
And fever turned me blue--
They said that I would be a
Dead man at twenty-two.
The aches and pains I thought
Were miseries a-plenty,
Compared to these, are naught;
And even these are bubbles,
That scarce can worry me,
When I regard the troubles
I'll have at twenty-three.
-- "The Shropshire Lad's Cousin"
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 |
 |
Taser Video 83.4 MB 7:26 min |
Pearly penile papules
Mumps orchitis
Gleason scale