MEN'S DISEASES
Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com

Cyberfriends: The help you're looking for is probably here.

Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected.

DoctorGeorge.com is a larger, full-time service. There is also a fee site at myphysicians.com, and another at www.afraidtoask.com.

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Freely have you received, give freely 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. Someday you may be able to access these pictures directly from this page.

I am presently adding clickable links to images in these notes. Let me know about good online sources in addition to these:

Freely have you received, freely give. -- Matthew 10:8. My site receives an enormous amount of traffic, and I'm handling about 200 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:

I've spent time there and they are good. Write "Thanks Ed" on your check.

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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 linked below. 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 presently have no sponsor.

This page was last updated February 6, 2006.

During the ten 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!

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More of Ed's Notes: Ed's Medical Terminology Page

Perspectives on Disease
Cell Injury and Death
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Fluids
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What is Cancer?
Cancer: Causes and Effects
Immune Injury
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Quackery
Alternative Medicine (current)
Alternative Medicine (1983)
Preventing "F"'s: For Teachers!
Medical Dictionary

Courtesy of CancerWEB

I used to pray, "Lord, give me chastity, but not yet!"

        -- St. Augustine, Confessions

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.

        -- Socrates

Iron John. Iron John. What MY wife wants is iron-ING John!.

        -- Anonymous man

{47692} index identifies this as "human male"
{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

Normal testis

WebPath Photo

Normal spermatogenesis

WebPath Photo

Male Histology
Ed's Histology Notes

Normal testis

WebPath Photo

Bart SimpsonWhile 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.

        --"Baghdad Betty", Iraqi disk jockey, during the Gulf War

Love, who is fairest among the immortal gods,
loosener of limbs, by whom all gods and all men
find their thoughts and wise counsels overcome in their hearts.

        --Hesiod

LEARNING OBJECTIVES

    Describe the following anatomic defects, how they arise, and what may happen as a result:

      Hypospadias
      Epispadias
      Phimosis
      Paraphimosis
      Peyronie's
      Pearly papules
      Hydrocele
      Varicocele
      Spermatocele

    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 Reiter's disease.

    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)

Male
Introductory Pathology Course
University of Texas, Houston

Male

Chaing Mi, Thailand

Men
Great pathology images
Indiana Med School

Penis Exhibit
Virtual Pathology Museum
University of Connecticut

Reproductive Disease
Mark W. Braun, M.D.
Photomicrographs

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.

      * There are a host of statistical differences in 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.

    Right now there is a pop "green" claim that hypospadias has doubled in frequency in the past twenty years, and the cause is chemical pollutants acting as "endocrine disruptors". The latest work shows no increase in either incidence or repair rates (Urology 57: 151, 2001; Env. Health Perspect. 108: 463, 2000); 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.

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. * 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).

      Balanoposthitis
      Little boy
      EMBBS

{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 (dx & rx Med. Clin. N.A. 74: 1543, 1990)

    Gonorrhea and "non-gonococcal urethritis" ("urethral syndrome", due to chlamydia, mycoplasma, trichomonas, perhaps 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.

    Reiter's disease (formerly "Reiter's syndrome"): the enigmatic triad of (1) arthritis involving many joints, (2) conjunctivitis, and (3) urethritis (for this handout, anyway). It's a man's disease and lasts for several months.

      The urethritis is usually (if not always) chlamydia, and one new study finds chlamydial RNA in the synovium (Arth. Rheum. 35: 521, 1992); if the initial episode of urethritis is treated appropriately, Reiter's is much less likely to ensue (Arth. Rheum. 35: 190, 1992).

      As with other "reactive arthropathies" (you may hear enteropathic arthritis called "Reiter's"), there's an impressive proliferation of T-cells specific for chlamydia within the affected joints (Arth. Rheum. 34: 588, 1991).

      Most patients are positive for HLA-B27.

      * Patients with Reiter's syndrome are likely to have circinate balanitis, keratoderma blennorrhagica 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.

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 a mess.

      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)

Warts
Male patient photos
Health Awareness Connection

    Genital herpes is familiar to you.

    Condyloma latum ("flat knob"): groups of flat-topped lesions that may ooze serous fluid; caused by secondary syphilis. Typically occur in skin folds.

    Pearly penile papules 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.

    Pearly penile papules
    Patient photo
    From a correspondent -- thanks

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.

    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
{46451} squamous cancer of the penis, with inguinal node metastasis

Cancer of the Penis
Dino Laporte's PathosWeb

Cancer of the penis
Clickable
WebPath Photo

Cancer of the penis
Clickable
WebPath Photo

PREMALIGNANT LESIONS OF THE PENIS

    Three diseases, all usually occurring in uncircumcised men.

    Erythroplasia of Queyrat: A raised, velvety plaque on the uncircumcised glans or prepuce.

      Histologic study shows dysplasia of the squamous epithelium. * Treatment is with topical 5-fluorouracil.

      A minority of cases (5-30%, estimaes vary) develop into squamous cell carcinoma if not removed.

{25095} erythroplasia of Queyrat, gross
{25096} erythroplasia of Queyrat, histology

    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.

      In many cases, the appearance of Bowen's disease on the skin heralds the growth of another malignancy internally.

    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
{25102} verrucous carcinoma, histology

I never trust a man unless I've got his pecker in my pocket.

        -- Lyndon Baines Johnson

When we've got them by the balls, their hearts and minds will follow.

        -- Charles Colson (pre-conversion), about the Vietnamese

Testis
Nice case photos
Charam M. Ramnani MD

Testis Exhibit
Virtual Pathology Museum
University of Connecticut

Testis I
From Chile
In Spanish

Testis II
From Chile
In Spanish

Slow-learner guy with large testes: Fragile X!

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, cryptorchidism, some cases of old age, after radiation, after some kinds of chemotherapy -- all will give a "Sertoli-only" histology) and unknown.

    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.

{00086} testicular atrophy, no sperms
{25154} testicular feminization (no sperms, hyperplasia of useless Leydig cells, why?)

Atrophic testis

WebPath Photo

Normal and atrophic testis

WebPath Photo

Testicular atrophy
Urbana Atlas of Pathology

Sertoli-Only
Good photos & discussion
Rockford Case of the Month

    * 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 a 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.

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:

    • The tubules will undergo atrophy and fibrosis, beginning in infancy and hopelessly advanced around puberty. There will be few or no germ cells, and the rete is also likely to fail to develop (Arch. Path. Lab. Med. 121: 1259, 1997).
    • There is an increased risk of torsion of the spermatic cord and gangrene of the testis.
    • The risk of germ cell cancer (usually seminoma) in undescended testes is around 30x greater than normal. Review Mayo Clin. Proc. 66: 372, 1991. The risk is also higher in previously-undescended testes. Even if the guy is an adult with no hope of having it rendered fertile, the testis needs to come down so he can check for tumors.
      • 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!

Epididymis Exhibit
Virtual Pathology Museum
University of Connecticut

    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: 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.

Mumps orchitis
Great photo
KU Collection

    Tuberculosis: granulomas involving the epididymis; may spread to the testis. * BCG epididymitis and orchitis: J. Urol. 148: 1534, 1992.

{25221} tuberculosis of epididymis

    Syphilis: gummas involving the testis; may spread to the epididymis.

TORSION OF SPERMATIC CORD ("torsion of the testis")

    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.

      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, which supposedly results in torsion after intermittent episodes of testicular pain (J. Urol. 148: 134, 1992). Current thinking also suggests spasm of the cremaster muscle plays a role.

      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?

    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!)

    * 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
{25208} torsion, gross
{10898} testes: normal vs. "atrophic" (could have been old torsion, old mumps, or whatever)

Torsion

WebPath Photo

GERM CELL TUMORS (cancer of the testis): Cancer of the germinal epithelium. These tumors are among the commonest solid tumors of young men. (Overall incidence is around 2/100,000 men.) Lance Armstrong

    Over 95% of tumors of the testis are malignant germ cell tumors. All about them (for pathologists): Am. J. Surg. Path. 17: 1075, 1993; Urol. Clin. N.A. 26: 595, 1999.

    Current thinking about the histogenesis of cancers of the testis emphasizes their common origin from germ cells:

    * Carcinoma in situ can usually be identified in nearby seminiferous tubules (Arch. Pathol. Lab. Med. 109: 555, 1985 for pictures). Embryonal carcinoma in situ: Arch. Path. Lab. Med. 126: 48, 2002. Microinvasive carcinoma: Cancer 70: 659, 1992. See below.

    All present as painless, non-tender masses in the testis.

    The primary may be occult, especially pure choriocarcinomas.

    Many cause gynecomastia (after puberty) or precocious puberty (children.)

    Risk factors for this disease are poorly understood. They include cryptorchidism and some intersex malformations (Arch. Path. Lab. Med. 114: 679, 1990). Familial cases: Mayo Clin. Proc. 65: 804, 1990. * Maternal DES exposure may be a factor.

      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.

        * 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.

      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).

    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.

        * Variant: spermatocytic seminoma of older men has somewhat different histology, no in situ phase, even better prognosis (i.e., it almost never metastasizes).

        * Tumors with more than 30 mitotic figures per 10 hpf and more likely to be aggressive (the old "anaplastic seminoma").

        Chorionic gonadotropin (hCG) is a tumor marker for the 50% 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").

{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

Seminoma

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Seminoma

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Seminoma

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Seminoma

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Lymphadenectomy incision
Supposedly belongs to
comedian Tom Green

Seminoma

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    * 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
Johnny Kruk

    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).

{23954} embryonal cell carcinoma, lumen of some kind and some wilder stuff
{23956} embryonal cell carcinoma; cartilage and erectile tissue (subtle)

Tom Green

Embryonal cell carcinoma

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Embryonal cell carcinoma

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Embryonal cell carcinoma

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      Many embryonal cell carcinomas also contain differentiated structures of a teratoma. (Teratoma + embryonal cell carcinoma = teratocarcinoma).

{25401} teratocarcinoma
{25402} teratocarcinoma

Teratocarcinoma

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Teratocarcinoma

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Mixture

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Teratocarcinoma

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    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).

    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.

      Or the cured metastases may turn into scar tissue, or just plain necrotic debris (J. Urol. 142: 1239, 1989).

      * Or curative chemotherapy can unmask a lethal sarcoma component or other cancer (Cancer 54: 1824, 1984).

    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 bleomycin, etoposide, and cisplatinum. (Formerly vinblastine took the place of etoposide.)

      * Chemotherapy for metastatic disease is so successful that some oncologists now prefer to monitor patients after surgery and give chemotherapy only if metastases appear. The most infamous after-effect of the traditional retroperitoneal lymph node dissection is 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. Some folks opt for just-chemotherapy instead, and Mayo's seems to think this could be the right idea... Mayo Clin. Proc. 70: 821 & 911, 1995).

      There are new procedures that prognosticate a non-seminomatous testicular carcinoma (especially with a focus on what percent of the tumor is embryonal-cell), and there's a nerve-sparing retroperitoneal lymph node dissection technique that supposedly leave the ability to ejaculate intact. Some centers now use nerve-sparing surgery-only, no chemotherapy (Urol. Clin. NA 25: 461, 1998).

      * Again, a two-year disease-free survival probably indicates cure. For more on chemotherapy and survival, see Cancer 67: 28, 1991.

    Choriocarcinoma:

      The bloodiest 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.

        In adults, it tends to be a component of an embryonal cell carcinoma.

      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, less good in adults.

{25175} yolk sac cancer, gross
{11551} yolk sac cancer, histology

Yolk sac carcinoma
Liver
Pittsburgh Pathology Cases

Yolk sac tumor

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    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).

    WARNING: Any tumor of germ cell origin may be mixed with any other tumor of germ cell origin.

    Mixed germ cell tumor of testis
    Great photos
    Pittsburgh Pathology Cases

      Further, any tumor of germ cell origin may metastasize as another histologic type of germ cell tumor. (Recently a seminoma turning into a yolk-sac tumor generated some surprise: Am. J. Clin. Path. 97: 468, 1992).

      We now know both in-situ and microinvasive testicular cancer. See Cancer 70: 659, 1992; Urol. Clin. N.A. 20: 127, 1993; Cancer 64: 715, 1989. A monoclonal antibody that stains carcinoma in situ: Cancer 65: 1135, 1990. * Currently, the trend seems to be to remove microinvasive cancer and radiate in-situ lesions.

      Lymphoma arises in the testes of older men with some frequency.

      Adenomatoid tumor is a benign, hard spherical nubbin, usually in the head of the epididymis, derived from mesothelium (* positive for EMA, cytokeratin).

      Germ-cell tumors (seminomas, embryonal cell tumors, teratocarcinomas, choriocarcinomas, and the usual mixtures) 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.

      The gross and microscopic appearances are typical for endocrine tumors. Sometimes, the pathologist can make the diagnosis easy by identifying a Reinke crystalloid!

      * Future pathologists: The tumor marker for Sertoli-Leydig differentiation is inhibin (Am. J. Surg. Path. 22: 615, 1998.)

      * 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).

    * Sertoli cell tumors ("androblastomas"; Urology 25: 1985; Am. J. Clin. Path. 96: 717, 1991), etc. Animal model Am. J. Path. 144: 454, 1994; Urol. Clin. N.A. 27: 529, 2000. Calcified sertolioma: think Peutz-Jegher's.

Leydig cell tumor
Pittsburgh Pathology Cases

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

Hydrocele

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    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.

Normal prostate
Cross-section
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Pathology of the Prostate
WebPath Tutorial

Normal prostate

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Normal prostate

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Prostate
Nice case photos
Charam M. Ramnani MD

Prostate Exhibit
Virtual Pathology Museum
University of Connecticut

Prostate gland
"Pathology Outlines"
Nat Pernick MD

Georgetown Med School
Prostate Pathology

Prostate I
From Chile
In Spanish

Prostate II
From Chile
In Spanish

PROSTATITIS

    You remember the normal gross and microscopic anatomy of the prostate gland.

      The lobes actually are only distinct in embryos.

      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
{25213} acute prostatitis, histology

      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
{25215} chronic prostatitis, histology

      In "non-bacterial prostatitis", the findings are as in chronic prostatitis, but no organisms grow. (Probably chlamydia 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 masturbating) makes this problem much worse (Int. J. Urol. 6: 130, 1999).

      "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 (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.

    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

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.

      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.

          "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 right now focuses on a various proteins produced by the stromal cells that causes hyperplasia of both glands and stroma (J. Urol. 147: 1444, 1992.)

      There's now 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.

    • Frequency (i.e., only small amounts are voided at a time), nocturia (urinating at night, same reason), difficulty starting and stopping urination, incontinence (dribbling), dysuria (painful urination), hernias (from straining), acute urinary retention (emergency)
    • Hematuria (due to stretching of veins), bladder hypertrophy and trabeculation (accentuation of the normal muscles), bladder diverticula, bladder stones, hydronephrosis, renal failure
    • Residual urine accumulates in an enlarged bladder behind the prostate gland. This gets infected, etc., etc.

    The treatment is surgical -- one favorite procedure is trans-urethral resection (TURP), or try the new laser approach (J. Urol. 154: 174, 1995) or the even newer cryosurgery or microwave techniques (pathology of cooked prostate: J. Urol. 171: 672, 2004; also J. Urol. 170: 12, 2003).  Hyperthermia: J. Urol. 144: 1390, 1990. How and when to intervene: Urol. Clin. N.A. 17: 509, 1990. 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.

{10743} prostate hyperplasia, gross. Don't try this paper clip trick at home.
{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

Benign Prostate Hyperplasia
Dino Laporte's PathosWeb

Prostatic Hyperplasia with Thick Bladder
Australian Pathology Museum
High-tech gross photos

Hyperplastic prostate

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TURP chips

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Median bar

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Prostatism
Hypertrophic bladder
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Hyperplastic prostate

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Hyperplastic prostate

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Prostate hyperplasia
Urbana Atlas of Pathology

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 androgen deprivation Cancer 68: 821, 1991; all about the disease Br. Med. J. 308: 780, 1994; Sci. Am. 279(6): 74, Dec. 1998. Frank Zappa

    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. The total number of people dying of the disease is actually decreasing slightly.

    The in-situ lesion (formerly "prostatic dysplasia", now "prostatic intra-epithelial neoplasia") is now well-characterized as well (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; some 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; 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). Usually these lesions will involve part of a single gland. Nowadays, the feeling is that PIN3 requires re-biopsy. For you future pathologists, here's how to make the call:

        Low grade

          PIN1: loss of secretion, piling up of cells ("tufting"), blue cytoplasm, looks lush

        High grade

          PIN2: As PIN1, but with high N/C ratio

          PIN3: As PIN2, but with prominent nucleoli and a papillary or cribriform pattern

          Any: The basal layer is at least somewhat intact.

            * 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. * 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. Most are "occult", however. Some more recent studies suggest that, after a man turns thirty, his percentage chance of having a little histological cancer is about the same as his age (J. Urol. 150: 37, 1993). All about those little microcarcinomas: Cancer 71(S3): 933 & 984, 1993. 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).

      Occult prostate cancers are common "incidental" findings in prostate chips obtained at turp.

        * 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.

      * Your lecturer suspects the 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).

      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).

        You remember the same claim about breast cancer in the 1980's; it didn't hold up.

      * Presently there's 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.

      * 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 beign prostate lesions, is PAX2 (J. Urol. 165: 2115, 2001). Expression of survivin, an apoptosis inhibitor, seems to predict poor prognosis: J. Uroo. 171: 18855, 2004. The tumor loses its androgen sensitivity when (Nowell's law!) the androgen receptor gene mutates (no surprise, NEJM 332: 1440, 1995). There is a prostate-cancer-family gene: HPC2 / ELAC2; curiously, it gives only about double the normal risk.

      * 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.

      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.

      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 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:

    • prominent nucleoli in nuclei with marginated chromatin (best; see Cancer 65: 1017, 1990)
    • invasion (especially perineural invasion; at least loss of the normal gland-stroma interaction); sometimes prostate cancer shows first as indian-files between the normal glands
    • obvious distortion of the architecture
    • loss of the outer layer ("basal layer") of the glands

        (* Future pathologists: you can use keratin 34βE12 ("keratin 903" or "K903"; most popular) or some other special keratin stain to see the basal layer; if absent or very discontinuous, think cancer)
    • Beware: As in breast, several benign lesions exist that are easily mistaken for cancer. Let us pathologists worry about these. Good reading: Am. J. Clin. Path. 101: 48, 1994.

      * 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.

    Grading of prostate cancer is now performed on the Gleason I-V system, based on low-power H&E pattern of tumor. Oversimplified Gleason's:

        I: Glands with some stroma between, sharp edge to the lesion

        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

        V: You can't really tell it's of glandular origin

      Gleason grading
      Online quiz
      Hopkins

      Grade correlates with stage and prognosis. Most prostate cancers, even the ones that have metastasized, are fairly well-differentiated adenocarcinomas.

        * Tissue prognostic indicators: Am. J. Clin. Path. 100: 256, 1993. Genetic prognostication (cyclin D1 and other cell-cycle kinases seem to be the key genes: Cancer 80: 753, 1997.) Biomarkers (microarray technology -- i.e., which genes are activated?): Nature 412: 822, 2001; Cancer 104: 209, 2005.

        * Gleason grading is not precise and there is considerable inter-pathologist variability: Arch. Path. Lab. Med. 129: 1004, 2005.

    * Staging of course also affects prognosis.

      For the TNM system --

        Tx: occult tumor

        T1: intracapsular, involves less than prostate

        T2: involves more than prostate

        T3: confined to prostate, but causes prostatic enlargement

        T4: extends beyond prostate

      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 endometrioid (J. Roy. Soc. Med. 85: 394, 1992; Acta Cytol. 35: 45, 1991), plus adenoidcystic, colloid, carcinosarcoma, signet-ring, oat-cell, carcinoid, and lymphoepithelioma.

    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, 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 -- oh no!) 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 is a new drug treatment for refractory bone pain -- it seems to work by preventing formation of new bone.

      * A recombinant cancer vaccine works for the rat model: J. Urol. 151: 622, 1994. Deep stuff.

      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.


{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

Prostatic intraepithelial neoplasia

WebPath Photo

Prostate cancer

WebPath Photo

Prostate cancer

WebPath Photo

Prostate cancer

WebPath Photo

Prostate cancer

WebPath Photo

Prostate cancer

WebPath Photo

Prostate cancer

WebPath Photo

Prostate cancer
PSA stain
WebPath Photo

Prostate cancer
Well-differentiated
Tom Demark's Site

Metastatic prostate cancer
Pittsburgh Pathology Cases

    * We've already cited the work of the Hopkins group, which (as in AIDS, renal disease, and coronary disease) found that black men with prostate cancer get worse care and do worse than their matched white counterparts. It turns out that another group (NCI, not Hopkins) found that if the same doctors treat both groups, the racial difference vanishes (JAMA 274: 1599, 1995; "I told you so....")

    * 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.

LOOKING AT PROSTATE BIOPSIES:

    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

A FEW ADDITIONAL IDEAS:

There is no difference between a wise man and a fool when they fall in love.

        -- Traditional

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. 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.

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, 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", and 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. "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. 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....

Penis fractured during vigorous sex

EMBBS

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.

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.

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, which by now are unequivocal. 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, Urol. Clin. N.A. 22: 57, 1995, Sci. Am. 1996, 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), 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 wilful, cruel abuse. The mohel may kiss the circumcision site and transmit herpes (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).

* 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. 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.

A Streetcar Named Desire

* 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. 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, or stay tuned for the next few lectures), and the forensic pathologist can make all the difference here. 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"); I am disturbed by the clear lack of scientific controls on this kind of work (not to mention a certain misandrism; J. Con. Clin. Psych. 58: 886, 1990; Arch. Sex. Behav. 20: 75, 1991; lots of things are turn-ons for lots of dudes, even us well-behaved ones: Arch. Sex. Behav. 20: 137, 1991. I envision a control group composed of people who have made political capital 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 appears utterly sincere, he is just told that he 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 recent 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 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 {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

* SLICE OF LIFE REVIEW

{00083} testes, normal
{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.

When I was one-and-twenty
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.

      -- A.E. Housman, "A Shropshire Lad"

* 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.

Now I am two-and-twenty,
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.

      Samuel Hoffenstein,
      -- "The Shropshire Lad's Cousin"

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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

Pathological Chess


Taser Video
83.4 MB
7:26 min