Prostate gland and seminal vesicles
21 July 2003, copyright © 2002-2003 PathologyOutlines.com, LLC
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Table of Contents
Prostate: normal, histology, prostatitis, prostatitis with eosinophils, malakoplakia, other infections, abscess
Granulomatous lesions: granulomatous prostatitis, allergic granulomatous prostatitis, post-TURP granulomas, TB-bCG granulomas
Benign lesions/conditions: amyloid, blue nevus, calculi, cystadenoma, ectopic prostate, endometriosis, extramedullary hematopoiesis, ganglioneuroma, infarct, inflammatory pseudotumor, leiomyoma, melanosis, Paneth cell-like change, postoperative spindle cell nodules, pseudosarcomatous fibromyxoid tumor, retention cysts, rhabdomyoma, signet ring nodule, urethral polyps, utricle cysts, venous thrombosis
Prostatic intraepithelial neoplasia/PIN: low grade PIN, high grade PIN, with adjacent small atypical glands
Prostatic carcinoma: general, histologic treatment effect, core biopsies, adenocarcinoma of peripheral ducts, grading, immunohistochemistry, atypical glands suspicious for malignancy, vanishing cancer phenomenon
Other carcinomas: adenoid basal cell tumor, adenosquamous, atrophic, atypical cribriform lesions, basaloid carcinoma, carcinosarcoma, clear cell adenocarcinoma, foamy gland adenocarcinoma, lymphoepithelial like carcinoma, mucinous (colloid), mucinous adenocarcinoma-bladder type, neuroendocrine, other primaries, prostatic duct carcinomas, pseudohyperplastic, signet ring, small cell, squamous cell, urothelial carcinoma
Microscopic mimics of prostatic carcinoma: adenosis/atypical adenomatous hyperplasia, atrophy, basal cell hyperplasia, clear cell cribriform hyperplasia, Cowpers glands, mesonephric remnant hyperplasia, mucous gland metaplasia, nephrogenic metaplasia/adenoma, paraganglion tissue, partial atrophy, post-atrophic hyperplasia, radiation changes, sclerosing adenosis, seminal vesicles / ejaculatory duct, squamous metaplasia, urothelial metaplasia, verumontanum mucosal hyperplasia, xanthoma cells
Sarcoma/lymphoma/other malignancies: angiosarcoma, embryonal rhabdomyosarcoma, leiomyosarcoma, lymphoma, malignant fibrous histiocytoma, PEComa, phyllodes tumor, PNET, solitary fibrous tumor, stromal proliferations of uncertain malignant potential, stromal sarcoma, synovial sarcoma, yolk sac
Miscellaneous: staging, features to report, grossing specimens
Seminal vesicles/Cowpers glands: normal, benign, carcinoma
American Journal of Clinical Pathology (AJCP), Dec 1971 to July 2002
American Journal of Surgical Pathology (AJSP), March 1977 to July 2003
Archives of Pathology and Lab Medicine (Archives), January 1976 to July 2003
Human Pathology (Hum Path), Nov 1978 to July 2003
Modern Pathology (Mod Path), Sept 1988 to July 2003
AJCC Cancer Staging Manual (6th Ed)
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999
Please refer to these primary references for more detailed discussions and photographs
Function: conduit for urine, adds nutritional secretions to sperm to form semen during ejaculation
20 g, funnel shaped, 4 x 3 x 2 cm
Within true pelvis between bladder neck (base of prostate) and urogenital diaphragm / levator ani muscle (apex of prostate)
Apex contains some muscle fibers from urogenital diaphragm
Seminal vesicles extend from posterior prostate to posterior surface of bladder
Ampulla of Vas (ductus) deferens and terminal seminal vesicle duct form ejaculatory duct, join prostatic utricle to open into prostatic urethra
Denonvillier’s fascia (aka rectovesicle septum): thin layer of connective tissue that separates prostate and seminal vesicles from rectum
Prostatic urethra begins on superior surface, descends almost vertically, with continuous prostatic utricle extending to posterior prostatic wall, exits anteriorly; divided into halves by sharp 35 degree angle midway, at site of verumontanum (bulge along posterior proximal urethra; site of emptying of ejaculatory, central and transition zone ducts)
Peripheral zone ducts empty into distal urethra
Prostatic nervous plexus supplies prostate, seminal vesicles, corpus spongiosum, corpora cavernosum and urethra; nerves distributed evenly in apex, mid gland and base of prostate, AJCP 2001;115:39
Anatomical models
Embryologic model: 5 lobes: 2 lateral plus posterior, middle, anterior lobes
Other model (not used): 2 lateral lobes, small median lobe (contains posterior lobe, forms floor of urethra)
Current model (McNeal): transition, central, peripheral, periurethral zones,
Outer (cortical) zones are termed “peripheral” and “central”; central is towards base
Inner (periurethral) zone is termed “transitional”
PSA
Glycoprotein; kallikrein related serine protease produced by secretory epithelium, drains into ductal system; cleaves and liquefies seminal coagulum formed after ejaculation
PSA > 4 seen in 80% with histologically documented cancer but also in 25-30% with nodular hyperplasia, prostatitis, infarcts, prostatic massage, cystoscopy; elevated in 2 of 18 post-race marathon runners, Archives 2003;127:345
Annual testing recommended for men 50+, men 40+ at increased risk
PSA density (PSA per volume of prostate gland), velocity (changes in PSA with time), %free (unbound to alpha-1-antichymotrypsin), serial measurements important for follow up
Reference: AJCP 1994;102 (4 Supp 1): S31
Transition zone
5% of prostatic volume; 2 pear shaped lobes surrounding proximal urethra
Site of nodular prostatic hyperplasia, may expand to bulk of gland
Site of 10% of prostate cancers (large duct carcinomas)
Contains moderately compact fascicles of smooth muscle
Central zone
25% of prostatic volume; surrounds transition zone to angle of urethra to bladder base
Site of 5% of prostate cancers
Unlike peripheral and transition zones, ducts are large and irregular; glands are complex with tall columnar, pseudostratified, papillary infoldings; striking basal cell layer with eosinophilic cytoplasm
Stroma is densest in central zone, least dense in peripheral zone, in between for transition zone
Reference: Hum Path 2002;33:518
Peripheral zone
70% of prostatic volume, from apex posterior to base, surrounds transition and central zones
Site of 80% of prostate cancers
Has loose fibromuscular stroma with widely spaced smooth muscle bundles, moderate gland complexity
Prostatic non-glandular tissue
“Capsule”: fibromuscular layer most prominent along base and posterior portion of lateral borders; an inseparable component of prostatic stroma, not a distinct capsule, AJSP 1989;13:21
Along lateral borders, fibrous septa traverse periprostatic fat and merges with fibromuscular stroma
Anteriorly, prostatic stroma merges with fibromuscular tissue of urogenital diaphragm
Stroma contains abundant smooth muscle, which duplicates function of myoepithelial cells in breast; i.e. squeezes out secretions
Prostatic glandular tissue
Prostate glands found normally within skeletal muscle at apex, anteriorly, and in distal posterolateral gland
Secrete normal mucins, produce pigment (lipofuscin), are androgen sensitive (castration causes atrophy); differentiation and growth is androgen dependent
Large prostatic ducts have single layer of urothelial-like epithelium without umbrella cells, which is PSA/PAP positive; may undergo squamous metaplasia with estrogen therapy
Benign tissue may contain hyaline globules (degenerative, aka thanatosomes, AJSP 2003;27:700), may be adjacent to skeletal muscle or nerves
Type of cells
secretory cells, basal cells, scattered neuroendocrine cells, urothelium, ejaculatory duct/seminal vesicle type cells
Secretory cells
Located along glandular lumen
Positive stains: prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), vimentin, keratin (some), Leu7, EMA (80%), CEA (25%)
Negative stains: CK903 (34 beta E12, high molecular weight keratin)
Basal cells
Separate secretory cells from basement membrane; consist of low cuboidal epithelium and columnar mucus secreting cells; may have prominent nuclear groove, prominent nucleoli
May be reserve cells (stem cells), can undergo myoepithelial metaplasia but are NOT myoepithelial cells
Their presence differentiates benign conditions (basal cells are present) from well differentiated adenocarcinoma (not present)
Positive stains: CK903 (34 beta E12 / high molecular weight keratin), p63, androgen receptors
Negative stains: PSA, PAP, S100, actin
Neuroendocrine cells
Irregularly distributed
Positive stains: chromogranin A, B, secretogranin II, peptide hormones, PSA
Negatives stains: androgen receptors
Urothelium
In proximal 2 mm of prostatic ducts
Ejaculatory ducts and seminal vesicles
Lined by double cell layer of pseudostratified epithelium, contain lipofuscin (golden-brown pigment), have large, hyperchromatic nuclei (also called "monster" nuclei), may have intranuclear inclusions
Mucins
Normal mucins are neutral; most adenocarcinomas secrete acidic and neutral mucins
Glandular secretions
Can identify with glutaraldehyde based fixatives, fill the normal secretory cell cytoplasm, distinct bright red on H&E staining because of high polyamine content; also present in penile urethra, Hum Path 2002;33:905
Diagnosis based on quantitative bacterial cultures and microscopic examination of fractionated urine specimens (first 10 ml of urine is urethral, midstream urine is from bladder) and expressed prostatic secretions
Definition: >10 WBC/HPF in prostatic secretions without pyuria; prostatic secretion cultures should have bacterial counts 10x urethral/bladder cultures
Clinical: elevated PSA
Treatment: difficult because antibiotics penetrate poorly into prostate
Micro: macrophages in stroma, neutrophils in ducts/acini are specific for acute prostatitis and usually localized; lymphoid aggregates are common with aging and nodular hyperplasia and not specific for prostatitis
DD of lymphoid aggregates: SLL/CLL
Acute bacterial prostatitis: same bacteria types as urinary tract infections (E. coli, gram negative rods, enterococci, staphylococci), usually due to reflux, also following surgical manipulation or sexually transmitted disease; usually localized, may cause obstruction, retention, abscess
Chronic bacterial prostatitis: symptoms of low back pain, dysuria, perineal and suprapubic discomfort; often have history of urinary tract infection by same organism; may have NO symptoms
Chronic abacterial prostatitis: similar clinically to chronic bacterial prostatitis but negative cultures; may be due to sexually transmitted disease organisms of Ureaplasma urealyticum, Chlamydia trachomatis, Mycoplasma hominis
DD: nonspecific granulomatous prostatitis, eosinophilic prostatitis, iatrogenic granulomas or parasitic infestation
May involve prostate, usually associated with bladder disease
Ages 47+
Represents a peculiar form of tissue reaction to bacterial infection
Usually periductal, may resemble carcinoma on ultrasound, may actually coexist with carcinoma
Prostate enlarged on clinical examination, suggestive of carcinoma
DD: nodular histiocytic prostatitis - similar but without Michaelis-Gutmann bodies
Dimorphic fungi associated with AIDS or other immunocompromise, usually with hematogenous dissemination
Chlamydia trachomatis and Trichomonas vaginalis often present (Archives 1986;110:430), but unknown if they are pathogens
AIDS related changes: epithelial cell apoptosis (simple cell shrinkage and exploding glandular cells), intracytoplasmic inclusions (apoptotic bodies) associated with lipofuscin, Archives 1998;122:875; increased numbers of concretions, AJCP 1990;93:196
Usually due to obstruction and E. coli; historically was often due to gonorrhea
Symptoms: acute urinary retention, perineal pain; prostate fluctuation on digital rectal exam
Diagnosis: transrectal ultrasound
Treatment: incision and drainage and antibiotics
Granulomatous lesions
Rare (< 1%) immune mediated reaction to prostatic secretions released from obstructed ducts
Usually associated with nodular hyperplasia in men age 50+
Symptoms: 20% have triad of high fever, prostatitis symptoms and hard prostate on digital rectal examination
Gross: stone hard to firm, obliterated architecture, yellow nodules
Micro: granulomas centered in lobules with multinucleated giant cells (30% of cases), epithelioid histiocytes, lymphocytes, plasma cells, fibrosis and eosinophils (may be prominent, Archives 1997;121:724); no organisms, no caseation
Early: mostly neutrophils and desquamated epithelial cells; late: granulomatous and chronic inflammatory cells
Positive stains: histiocytes for lysozyme
Negative stains: PSA/PAP in histiocytes (AJCP 1991;95:330)
DD: carcinoma (primary, metastatic), acid-fast bacilli, fungi, BCG treatment of bladder, post TURP
Allergic granulomatous prostatitis
Very rare ( <20 reported cases)
Reflects asthma or systemic allergic reaction; often serum eosinophilia, systemic granulomas
Treatment: steroids
Micro: multiple small, necrobiotic granulomas surrounded by numerous eosinophils; diffuse stromal eosinophils
DD: Post-TURP granulomas with eosinophils (more irregular granulomas, eosinophils not diffuse)
Formerly eosinophilic prostatitis
No systemic symptoms, develop months to year after TURP or rarely after needle biopsy
Occur after cautery in other sites
Hair granuloma: post-TURP, hair probably embedded in prostate by earlier needle biopsy, Hum Path 1996;27:196
Micro: central region of fibrinoid necrosis surrounded by pallisading histiocytes; resembles rheumatoid nodules; long tortuous granulomas may dissect tissue; minimal surrounding inflammation (lymphocytes, plasma cells, rare eosinophils); more eosinophils in first month after TURP, AJSP 1984;8:217
Tuberculosis and bCG-related granulomas
Tuberculosis
Prostate is most common site for tuberculosis in male GU tract (involved in >90% of cases with GU involvement), due to hematogenous spread from lungs or direct invasion from urethra
May perforate into urethra and extend into bladder or rectum
May calcify or become small and fibrotic, resembling carcinoma
Diagnosis: fluctuant, tender zones, usually bilateral, on digital rectal examination
bCG
Due to intravesical treatment with bacillus Calmette-Guerini for bladder carcinoma
Causes caseating or non-caseating granulomas; usually AFB negative
Located along periurethral or transition zone or diffuse
No specific therapy required, although rarely disseminates as tuberculosis
Aka benign prostatic hypertrophy
Periurethral nodules may compress urethra and cause obstructive symptoms
Present in 20% of men at age 40, 50% at age 50, 70% at age 60
No correlation between histology and symptoms (50% with histologic disease have clinical enlargement of prostate, 50% of these have symptoms)
Recommended to not use this diagnosis on biopsies due to lack of correlation with obstructive symptoms; however presence of stromal nodules does correlate with increased prostatic weight, Hum Path 2002;33:796
Physiology: requires intact testes; testosterone and dihydrotestosterone (DHT, 10x more potent than testosterone because it dissociates from receptor more slowly) bind nuclear androgen receptors in stromal and epithelial cells, causing growth factor activation
Stromal cells produce 5 alpha reductase (converts testosterone to DHT)
Estradiol, increased in aging men, may also increase androgen receptors
Symptoms: urinary tract infection, obstruction, acute urinary retention, bladder hypertrophy, trabeculation, diverticula
NOT associated with prostatic adenocarcinoma, although it may develop in residual gland after TURP
One study showed transition from nodular hyperplasia to transition zone adenocarcinoma in some cases, Hum Path 2003;34:228
Treatment: transurethral resection of prostate (TURP, #2 most common surgery after cataracts in men > 65, 400,000 per year in US); suprapubic prostatectomy; androgen antagonists, smooth muscle relaxers (5 alpha reductase inhibitors decrease DHT and in many cases, prostatic volume and symptoms)
Note: may recur after TURP as peripheral tissue expands to surround the prostatic urethra
Gross: large, discrete, periurethral nodules; mean size of surgical prostatectomy specimens is 100g; usually in transitional and periurethral zones (5% in peripheral zone), although enlarged prostate may compress other zones; glandular hyperplasia is yellow-pink, soft, oozing prostatic fluids; stromal hyperplasia is gray, tough
Micro: Hyperplasia of glandular and stromal tissue with papillary buds, infoldings and cysts; associated with squamous metaplasia and infarction; begins around urethra where ejaculatory ducts enter (transitional or periurethral zone); basal cell layer is continuous; stromal changes are increased smooth muscle, less elastic tissue, lymphocytes around ducts (not associated with infectious process or prostatitis in most cases)
Variations include sclerosing adenosis, fibroadenoma-like and phyllodes-like hyperplasia, leiomyoma-like nodules, fibromyxoid nodules, associated with infarct
Positive stains: CD10 (Hum Path 2003;34:450)
Benign or non-neoplastic conditions of prostate and prostatic urethra
Vascular amyloid deposits are present in 2-10% of prostates with nodular hyperplasia or adenocarcinoma
Higher incidence of amyloid deposits in patients with myeloma, primary amyloidosis of kidney or chronic diseases
Amyloid usually subepithelial or vascular
Note: corpora amylacea may stain nonspecifically for amyloid
Melanin confined to ovoid melanocytes in S100+ prostatic stroma (probably melanocytes), not glands
EM: melanin present in mature melanosomes
Reference: AJCP 1988;90:530
Identified in 7% of prostates with nodular hyperplasia
Stones usually contain phosphate salts of calcium, magnesium, potassium, calcium carbonate or calcium oxalate
Corpora amylacea may act as nidus for stone formation
Radioopaque, are detected by Xray
Rarely are infected and cause abscesses
Treatment: prostatectomy may be required for large calculi
Gross: brown-gray, round-ovoid, usually smooth surface
Micro: stratified in concentric layers resembling calcified corpora amylacea
DD: carcinoma (both hard), prostatic urethra calculi from bladder, ureter or renal pelvis
Case reports in men age 28 and 37 at AJSP 1991;15:131
May extend into retroperitoneum and be attached to prostate by a small pedicle
May be termed ectopic prostate if detached from prostate
Benign behavior
Micro: large, multilocular mass of glands/cysts lined by prostate-type epithelium in hypocellular fibrous stroma
Positive stains: PSA, PAP
DD: nodular hyperplasia
Very rare, < 10 cases described
Case report #1: presacral mass in 78 year old man, Archives 2001;125:286
Case reports #2-6: ectopic prostatic tissue in uterine cervix, AJSP 2001;25:1215
Cervical cases were incidental (2 patients) or present in cone biopsy for high grade dysplasia
May be similar to multilocular prostatic cystadenoma, although distinct from prostate
Prostatic differentiation in ovarian mesonephric remnants has also been described, AJSP 1999;23:232
Micro: ducts and acini, some papillary or cribriform, with prominent squamous metaplasia
Positive stains: PSA, PAP, high molecular weight keratin (for basal cells)
Endometriosis
Case report in 78 year old man after long course of estrogen therapy, AJSP 1985;9:374
Extramedullary hematopoiesis
Rare, case report of 75 year old man with myelofibrosis and bladder outlet obstruction
TURP revealed atypical megakaryocytes, immature granulocytes and normoblasts in prostatic stroma, AJSP 1991;15:486
Rare, case report associated with neurofibromatosis, Archives 1994;118:938
Mean age 71; usually associated with nodular hyperplasia in TURP specimens, not needle biopsies
Usually clinically silent, may cause acute urinary retention due to associated edema; may cause gross hematuria if adjacent to urethra; may cause marked PSA elevation that returns to normal after removal of infracted tissue
Causes: trauma, catheter, cystitis, prostatitis
Gross: variable size; speckled, gray-yellow, with streaks of blood and sharp peripheral margins
Micro: ischemic type infarcts with sharply outlined areas of coagulative necrosis of glands and stroma
May see prominent squamous metaplasia with mitotic figures at the periphery of the infarct (but no keratinization, no pleomorphism, localized to area of infarct only); cyst formation often present within glands, corpora amylacea and collagenous rings present around metaplastic glands; zonation is present, but may not be appreciated by needle biopsy
DD: necrosis from infectious granulomas, post-biopsy granulomas (fibrinoid necrosis surrounded by pallisading epithelioid histiocytes), squamous and urothelial carcinoma
Reference: AJSP 2000;24:1378
Similar to bladder tumor
Micro: myxoid stroma, granulation tissue vascularity, inflammatory cells
May be difficult to distinguish from nodular hyperplasia (no well organized fascicles, no hyalinization, no necrosis, no calcification)
Melanin containing elongated cells in prostatic stroma and glands; presence in glands probably derived from stroma, AJCP 1988;90:530
Positive stains: S100 (melanocytes)
EM: melanosomes
DD: lipofuscin in prostate (golden yellow-brown to gray-brown granules, positive for Fontana-Masson, PAS with diastase, Congo red, Luxol fast blue, oil-red-O and Ziehl-Neelsen stains; bleached by permanganate, negative for Prussian blue AJSP 1994;18:446; Mod Path 1996;9:791)
Associated with both benign and malignant lesions, Archives 1992;116:1101
Collections of prostatic cells with eosinophilic granules resembling intestinal Paneth cells, AJSP 1992;16:1013
Represents either (a) PAS-positive and diastase-resistant eosinophilic cytoplasmic granular change in benign prostatic epithelium, or (b) endocrine differentiation with neuroendocrine granules in dysplastic and malignant prostatic epithelia, AJSP 1992;16:62
Positive stains: PAS, diastase resistant (benign epithelium), neuroendocrine markers (dysplastic/malignant epithelium)
EM: exocrine-like or lysosomal-like vesicles in benign epithelium, neuroendocrine granules in dysplastic / malignant epithelium
Postoperative spindle cell nodules
Exuberant stromal reaction occurring weeks to months after TURP that resembles a sarcoma and may cause postoperative bleeding
Gross: friable red nodules, resembling granulation tissue or sarcoma
Micro: cellular with high mitotic activity; intersecting fascicles of spindle cells with extravasated red blood cells resembling Kaposi’s sarcoma; minimal nuclear pleomorphism, no atypical mitoses; relatively small size
Positive stains: keratin (strong), actin (variable)
Negative stains: EMA
Pseudosarcomatous fibromyxoid tumor
Rare, resembles sarcoma or sarcomatoid carcinoma
Similar to postoperative spindle cell nodule but without history of TURP
Diploid, low S phase fraction
Benign behavior
Micro: myxoid lesions, proliferation of spindle fibroblastic cells in a background of granulation tissue-type vascularity and inflammatory cells; rare mitoses, no atypical mitoses
Positive stains: vimentin, smooth muscle actin
Negative stains: S-100, desmin, myoglobin, keratin
EM: fibroblastic and myofibroblastic cell features
References: Hum Path 1993;24:1203
Symptomatic cysts, 1-2 cm, usually unilocular, adjacent to urethra
Lined by flattened prostatic glandular epithelium or urothelium
Case report, Archives 2000;124:1518
More common in vulva of young women
3 cases reported in men, one from prostate, one from testis, one from epididymis
Micro: stromal nodule with short spindly cells with bland nuclear features, but also large, clear cytoplasmic vacuoles in many cells resembling signet-ring carcinoma cells but non-infiltrative
Positive stains: vimentin, desmin (weak)
Negative stains: mucin
References: AJSP 2002;26:1066
Common cause of hematuria in young adults
Benign
Treatment: transurethral fulguration
Gross: single, villous, polypoid lesions in verumontanum and posterior-lateral urethra
Micro: tall columnar cells of prostatic origin, may have nephrogenic (adenomatoid) appearance; may coexist with carcinoma; papillary projections often contain prostatic stroma and glands; broad fingerlike projections differ from delicate fibrovascular cores of papillary urothelial carcinoma
Positive stains: PSA, PAP
Cytology: bland columnar cells with uniform oval nuclei, Archives 2000;124:1047; prostatic adenocarcinoma can also present as a urethral polyp
DD: villous polyps (dysplastic epithelium resembles colonic adenomas, are actually papillary prostatic duct adenocarcinomas)
References: AJCP 1975;63:343, AJSP 1983;7:351
Utricle cysts
Usually between bladder and rectum, with cyst orifice at prostatic utricle
Mean age 26 years (range 2 months to 75 years)
Associated with abnormal external genitalia in 25%, unilateral renal agenesis/dysgenesis in 10%
Cysts contain calculi in 10%; epithelial lining is variable or missing
Mast cells are present in increased numbers in adventitia of thrombosed veins; may have a role in endogenous fibrinolysis, AJCP 2001;116:97
Prostatic intraepithelial neoplasia (PIN)
Common finding in young men
Recommended to NOT put on surgical pathology report since variability in diagnosis exists even between experts, AJSP 1995;19:873
Micro: more architectural complexity than hyperplasia, occasional enlarged nuclei, rare nucleoli, usually diploid
Present in 14% of patients in a community hospital study
Indicates 33% risk of carcinoma in subsequent biopsies
Low risk for cancer (13%) if two subsequent biopsies are negative
Number of cores with high grade PIN predicts risk of subsequent cancer (1 core-30%, 3 cores-40%, 4+ cores-75%), predominantly cribriform/micropapillary patterns also predict higher risk, AJSP 2001;25:1079
In Americans less than 60 years old, more common in blacks vs. whites
Does not cause elevated PSA
If found on TURP specimen, should examine all submitted tissue for invasive adenocarcinoma
50% are aneuploid
Micro: low power diagnosis; usual patterns are micropapillary / cribriform (70%), flat / tufted (20%); basophilic appearance at low power due to enlarged hyperchromatic nuclei and amphophilic cytoplasm; may develop tall papillary tufts; frequently multicentric in prostatectomy specimens
Identifiable on low power as glands with (a) papillary projections into lumina, (b) hyperchromasia, (c) enlarged nuclei, (d) pleomorphism, (e) stratification/crowding, (f) prominent nucleoli
Cells may contain pigment, may have intraluminal mucin staining similar to invasive carcinoma
Positive stains: basal cells - CK903, p63, CD10 (Hum Path 2003;34:450), secretory cells - P504S/AMACR (AJSP 2003;27:772)
DD: seminal vesicle glands with cribriform epithelium and no atypia (normal findings);
clear cell cribriform hyperplasia (clear cytoplasm, benign nuclei, no/small nucleoli, prominent basal cell layer),
central zone glands (base of prostate adjacent to seminal vesicles; usually cribriform or Roman arch formation at end of core biopsy; tall columnar cells with eosinophilic cytoplasm, prominent basal cell layer; associated thick muscle bundles of bladder neck, no cytologic atypia, Hum Path 2002;33:518)
High grade PIN patterns
Apocrine, cribriform, flat, foamy gland, inverted (hobnail), micropapillary, mucinous, Paneth cell-like, pleomorphic, signet-ring cell, small cell neuroendocrine, tufting
Cribriform pattern
Flat pattern
Foamy gland pattern
Micro: pale/foamy cells with voluminous xanthomatous cytoplasm, forming solid and cribriform patterns
Inverted (hobnail) pattern
Localized to peripheral zone, AJSP 2001;25:1534
Associated with concurrent prostatic adenocarcinoma in 50% of cases
Micro: polarization of enlarged secretory cell nuclei toward the glandular lumen; merges with typical micropapillary–tufted HGPIN; often less prominent nucleoli than adjacent noninverted secretory cell nuclei
Micropapillary pattern
Mucinous
Micro: mucinous distension of glands with flat epithelial lining, blue mucinous secretions
Positive stains: PAS, Alcian blue, AJSP 1997;21:1215
Pleomorphic pattern
Micro: pleomorphic nuclei, although nucleoli may not be prominent
Signet ring pattern
Micro: associated with primary signet ring cell carcinoma
Positive stains: PSA
Negative stains: mucin negative, AJSP 1997;21:1215
Small cell pattern
Associated with primary small cell carcinoma
Positive stains: chromogranin, synaptophysin, neuron-specific enolase, AJSP 1997;21:1215
Tufting pattern
High grade PIN with adjacent small atypical glands (PINATYP)
May be difficult to determine if small glands represent budding / tangentially sectioned glands from high-grade PIN or invasive cancer next to high grade PIN; no reliable differentiating features
Risk of cancer on repeat biopsy was 46%, higher than high grade PIN alone, indicating patients should be rebiopsied, Hum Path 2001;32:389
Prostatic carcinoma-general
Epidemiology: 300,000 cases/year in US (#1 after skin cancer), 41,000 deaths/year (#2 after lung cancer)
20% of American men are diagnosed with prostate cancer during their lifetimes; 3% die of prostate cancer
Age adjusted incidence is increasing
99% with clinical disease are age 50+
Latent cancers: 20% in men in 50’s, 70% in men in 70’s; usually must examine entire gland to find; rarely metastasize, Archives 1995;119:731
Clinical disease and high grade prostatic intraepithelial neoplasia (PIN) more common in blacks than whites with higher stage at presentation; stage adjusted survival is similar
Clinical disease rare in Asians (3-4/100,000 vs 50-60/100,000 among US whites); higher rates in Scandinavians; all groups have similar incidence of latent cancers, suggesting importance of environmental or other genetic factors
No carcinoma if pre-pubertal castration, low incidence with hyperestrogenism (liver cirrhosis)
Case report of prostatic adenocarcinoma in karyotypic female with congenital adrenal hyperplasia due to 21-OHase deficiency, AJCP 1996;106:660
Not associated with sexually transmitted disease, smoking, occupational exposure, diet, nodular hyperplasia
Clinical: detect with rectal exam, transurethral ultrasound (misses 30% of carcinomas that are isoechoic), elevated PSA (above 4 or increasing over time)
Note: prostate carcinomas secrete 10x the PSA of normal tissue (in the past, 50% had levels > 10 mg/ml)
DD of firm prostate is granulomatous prostatitis, nodular hyperplasia, tuberculosis, infarct, lithiasis
DD of elevated PSA is nodular hyperplasia (mild increase in PSA), prostatitis, infarct, trauma (biopsy, TURP), rarely other tumors (case report of salivary duct carcinoma, AJCP 1996;106:242); for benign disease, increase in PSA is usually transient
Histologic treatment effect
Estrogen therapy
Causes cytoplasmic vacuolization, nuclear pyknosis, naked nuclei; also squamous metaplasia of normal and malignant glands
LHRH agonists and flutamide
Cause striking vacuolization of tumor cells and benign cells; nuclear pyknosis, squamous metaplasia, atrophy with prominence and hyperplasia of basal cell layer; may cause pseudomyxoma ovarii type changes of minute to large pools of extravasated basophilic acid mucin dissecting through prostatic stroma with an infiltrative appearance on low power; secretions positive for mucicarmine, Alcian blue (pH 2.5), PAS after diastase; no basal cells present, AJSP 1998;22:347, AJSP 1996;20:86, AJSP 1994;18:979, AJSP 1991;15:111; high grade PIN persists after endocrine treatment, Hum Path 1999;30:1503
Difficult to evaluate margin status after androgen deprivation
Antiandrogen cyproterone acetate
Micro: normal prostate showed atrophy, basal cell hyperplasia and prominence; adenocarcinoma showed reduced cytoplasmic, cytoplasmic vacuolation, nuclear pyknosis, reduced gland diameter, mucinous breakdown; often collagenous stroma obscuring malignant glands; recommended to NOT give a Gleason grade to these specimens.
References: AJSP 2002;26:1400
External beam therapy
Clinician may NOT be aware of treatment history
Causes effects on vascular, stromal and epithelial compartments
Vascular: arterial luminal narrowing due to myointimal proliferation and thrombi, foam cells in vessel walls, vascular hyalinization
Stroma: stromal fibrosis
Epithelium: no or marked cytologic atypia; also glandular atrophy with scant eosinophilic cytoplasm and small pyknotic nuclei, basal cell prominence, Paneth cell-like change, squamous and mucinous metaplasia, blue-tinged mucinous secretions,