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    Slide 1

    Prostate Pathology

    Martha K. Terris, M.D.

    Medical College of Georgia

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    Slide 2

    Normal

    Complex glands with 2 cell layers, epithelial

    and basal cell layers

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    Slide 3

    Normal

    Complex glands with 2 cell layers, epithelial

    and basal cell layers, no nucleoli

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    Slide 4

    Normal

    HMW keratin stains basal layer

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    Slide 5

    BPH

    Occurs in Transition Zone

    Due to androgen stimulation & estrogen synergism

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    Slide 6

    Histologic features: both glands and stroma can become hyperplastic cytologically benign with 2 cell layers, bland nuclei and

    abundant cytoplasm nonspecific chronic lymphocytic infiltrate is common

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    Slide 7

    BPH

    Stromal Hyperplasia

    Theorized to respond better to alpha-

    blockade

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    Slide 8

    Corpora amylacea may be identified (laminatedeosinophilic concretions within the lumen of the gland)

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    Slide 9

    BPH

    Basal Cell Layer not always easy to identify

    Slid 10

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    Slide 10

    BPH

    HMW keratin staining may show gaps in

    basal layer but will always be at least partial

    Slid 11

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    Slide 11

    BPH

    Like normal prostate tissue, nucleoli are nottypically identified

    Slid 12

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    Slide 12

    BPH

    Branching glands, corpora amylacea, nonucleoli

    Slid 13

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    Slide 13

    BPH

    Nodule of glandular hyperplasia

    Theorized to respond better to finasteride

    Slide 14

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    Slide 14

    BPH

    Nodule of glandular hyperplasia

    Theorized to respond better to finasteride

    Slide 15

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    Slide 15

    BPH

    Nodule of glandular hyperplasia

    Glands can be dilated with secretions

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    Slide 16

    BPH

    Nodule of glandular hyperplasia

    Glands can be dilated with secretions

    Slide 17

    P l id H l i

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    Slide 17

    Polypoid Hyperplasia

    Aka Prostatic urethral polyps; Present with hematuria Small polyps demonstrating typical prostatic-type

    epithelium; PSA and PAP positive; behavior is benign andrecurrence after TUR is unusual.

    Histology can also be adenomatoid (nephrogenic adenoma;frequent recurrence) and adenomatous (endometroid)

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    Slide 18

    Infarcts

    20-25% of BPH specimens have infarcts Patients may present with acute retention due to a

    sudden increase in the size of the prostate

    Gross: mottled and yellowish, or may appear

    hemorrhagic

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    Slide 19

    Infarcts

    Histologic features: typically shows three zones central zone of coagulative necrosis (everything looks

    reddish with faint outlines of the cells, like ghost cells) middle zone of hemorrhage and inflammation

    peripheral zone of glands with squamous metaplasia

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    Slide 21

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    Slide 21

    Acute Prostatitis

    Inflammatory infiltrate within gland lumens

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    Slide 22

    Chronic Prostatitis

    Inflammatory infiltrate surrounds the glands,involving the surrounding stroma

    Slide 23

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    Slide 23

    Acute and Chronic Prostatitis

    Infiltrate both in lumens and surrounding

    glands

    Slide 24

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    Slide 24

    Malignant Lymphoma

    Diffuse infiltration of parenchyma by small roundblue cells with minimal cytoplasm

    Typically the normal architecture is spared

    Stains for leukocyte markers are positive

    Slide 25

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    PIN

    Probable precursor lesion for prostatic carcinoma Divided into low grade (mild dyplasia/ grade I) and

    high grade (moderate dysplasia/ grade 2 and severedysplasia/ grade 3)

    High grade PIN is a marker for cancer Histologic features:

    on low power, the glands appear large and complex, butmore basophilic (blue) than the normal glands of BPH

    basal cells are present, if only focally

    high power shows prominent nucleoli, nuclear crowdingand pseudostratification (piling up of the nuclei)

    also: the papillary structures at low power turn out to becaused by the cellular pile-up; in BPH, the papillarystructures actuallly have fibrovascular cores and therefore

    are true papillae.

    Slide 26

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    PIN

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    PIN

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    Normal Gland and PIN

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    PIN

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    PIN

    Papillary lumenal projections have NO

    fibrovascular core

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    Compare to BPH

    Papillary structures each have afibrovascular core

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    Low Grade PIN

    Multiple epithelial cell layers but unlike highgrade PIN, has no nucleoli

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    High Grade PIN

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    High Grade PIN

    HMW keratin shows fragmented basal cell

    layer

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    Beware: Basal Cell Hyperplasia

    Nuclei are ovoid with finely reticular chromatin andrare punctate nucleoli. The cytoplasm is paleeosinophilic or clear

    Slide 36

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    Basal Cell Hyperplasia

    Slide 37

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    Basal Cell Hyperplasia

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    Prostate Adenocarcinoma

    Microscopic foci of cancer may begin in the30s, present in 70% of men by the age of 70

    80% occur in the peripheral zone, 10-20% inthe transition zone; most appear yellow or

    gray-white grossly Histologic features:

    Unlike other malignancies, neoplastic glands arevery small, simple, and bland. Complexity in theprostate is generally a good sign, whereas smallsimple glands may herald cancer.

    helpful findings: blue mucin, crystalloids,prominent nucleoli, single layer of cells (immuno)

    Gleasons grading system

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    Prostate Cancer Crystalloids

    Elongated, refract light

    Corpora

    amylacea

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    Prostate Cancer Blue Mucin

    Slide 41

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    Prostate Immunohistology Alpha-methylacyl-CoA-racemase (racemase) aka,

    P504S, is an enzyme involved in beta-oxidation of branchedchain fatty acids. Moderate to strong staining is seen inprostate cancer and high-grade PIN, but not in benignprostatic tissue.

    HMW cytokeratin antibody (34-E12) stains the cytoplasm

    of basal cells of the prostate. Increasing grades of PIN areassociated with progressive disruption of the basal celllayer. Cancer cells consistently fail to react with thisantibody.

    p63 antibody stains the nucleus of basal cells. Basal cell

    cocktail (34 -E12 and p63) increases the sensitivity of thebasal cell detection and reduces staining variability, thusrendering basal cell immunostaining more consistent.

    PSA, PAP antibodies are useful in cases of unknownprimary or very de-differentiated tumors.

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    Prostate Immunohistology

    HMW keratin and p63 stain basal cell layer of atrophicbenign gland

    Racemase stains malignant cells

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    Gleason Grade Gleason grading assigns prostatic malignancy a

    rank from 1 to 5 based on level of dedifferentiation.1 being best. 1 and 2 are rarely used any more soreally a rank from 3-5

    Prostatic cancers are typically heterogenous

    therefore receive the sum of their two mostcommon architectural patterns the first number is the most prevalent pattern the second number is the second most prevalent pattern

    (a minimum of 10% of the cancer volume)

    Denoted the two numbers separately is the Gleasonscore, i.e. 4+3 the sum of the two, e.g., 7 is the Gleason sum or grade

    and is an excellent predictor of clinical behavior. Sometimes a tertiary grade will be mentioned (or used as

    the secondary grade) if it is poorly differentiated.

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    Grades 1-3 consist of small, simple round glandswith a single cell layer surrounded by stroma Grade 1: Glands in nodular pattern Grade 2: Glands in vaguely rounded configuration

    Grade 3: Glands infiltrating between normal glands

    Grade 4: Fused glands (no stroma separating someof the glands) or multiple lumens in a single gland.

    Grade 5: No longer attempting to create glands; cells

    in sheets, clumps, rows, or individual.

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    Gleason Grading

    Do not try to assign a grade totreated tissueHormone therapyPrior radiation therapy of any kind

    Slide 46

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    Gleason Grade 1

    nodules of uniform, closely-packed malignantglands, nucleoli are relatively inconspicuous

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    Gleason Grade 2

    Nodular configuration but more looselypacked.

    Slide 48

    G G

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    Gleason Grade 2

    Nodular configuration but more looselypacked.

    Slide 49

    Gl G d 3

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    Gleason Grade 3

    Tumor infiltrates in and among the non-neoplastic prostatic glands

    Slide 50

    Gl G d 3

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    Gleason Grade 3

    Tumor infiltrates in and among the non-neoplastic prostatic glands

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    Gl G d 3

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    Gleason Grade 3

    Tumor infiltrates in and among the non-neoplastic prostatic glands

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    Gl G d 4

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    Gleason Grade 4

    Fused glands without completely surrounding

    stroma, poorly formed or multiple lumens

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    Gl G d 4

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    Gleason Grade 4

    Fused glands without completely surrounding

    stroma, poorly formed or multiple lumens

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    Gl G d 4

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    Gleason Grade 4

    Fused glands without completely surroundingstroma, poorly formed or multiple lumens

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    Gl G d 4

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    Gleason Grade 4

    Fused glands without completely surroundingstroma, poorly formed or multiple lumens

    Slide 56

    H h id Gl G d 4

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    Hypernephroid Gleason Grade 4

    Abundant clear cytoplasm with a dot-likenucleus

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    M i Gl G d 4

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    Mucinous Gleason Grade 4

    Extracellular mucin makes up at least 25% of

    tumor volume

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    Gl G d 5

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    Gleason Grade 5

    Minimal gland formation, cells in sheets,

    clumps, cords

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    Gl G d 5

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    Gleason Grade 5

    May need PSA stain to confirm diagnosis

    Slide 60

    Gl G d 5

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    Gleason Grade 5

    Minimal gland formation, cells in sheets,

    clumps, cords

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    Gleason Grade 5

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    Gleason Grade 5

    Minimal gland formation, cells in sheets,

    clumps, cords

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    Gleason Grade 5

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    Gleason Grade 5

    Signet Ring Histology

    Slide 63

    Cribriform

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    Cribriform

    Smoothly-circumscribed nodules with large ductsthat are filled and distended with tumor in acribriform pattern can be called grade 3 or 4. Thepresence of central necrosis in a cribriform

    carcinoma raises the grade to 5.

    Slide 64

    Gleason Grade 5

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    Gleason Grade 5

    Grade 5 Cribiform with comedonecrosis

    Slide 65

    Seminal Vesicle

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    Seminal Vesicle

    Beware of trick questions!

    Slide 66

    Seminal Vesicle

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    Seminal Vesicle

    Look for golden-brown granules of

    lipofuscin pigment

    Slide 67

    Small Cell Carcinoma

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    Small Cell Carcinoma

    Small round blue cells in sheets, necrosis, high mitotic rate.

    Molded nuclei with inconspicuous nucleoli

    PSA and PAP stains are typically negative and serum PSAlevels may be only mildly elevated. Neuroendocrine stains

    positive

    Slide 68

    Endometroid Carcinoma

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    Endometroid Carcinoma

    Typically arises in area of urethra/prostatic utricle

    PSA and PAP positive

    Often grade 3 or 4 but 5 if has necrosis

    Slide 69

    Transitional Cell Carcinoma

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    Transitional Cell Carcinoma

    Typically involves large ducts

    More cytologic atypia than prostate cancer

    PSA negative

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    Squamous Cell Carcinoma

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    Squamous Cell Carcinoma

    Rare in North America, more often in areaswhere Schistosomiasis is endemic

    Histologic features include keratin pearl

    formation, intercellular desmosomes, etc.

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    Rhabdomyosarcoma

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    Rhabdomyosarcoma

    Average age 7 years, rapid growth

    Sheets of small round blue cells with scatteredstrap cells (tadpole cells) having cross-striations