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Prostate Pathology
Martha K. Terris, M.D. Medical College of Georgia

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Normal

Complex glands with 2 cell layers, epithelial and basal cell layers

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Normal

Complex glands with 2 cell layers, epithelial and basal cell layers, no nucleoli

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Normal

HMW keratin stains basal layer

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BPH

Occurs in Transition Zone Due to androgen stimulation & estrogen synergism

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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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BPH

Stromal Hyperplasia Theorized to respond better to alphablockade

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

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BPH

Basal Cell Layer not always easy to identify

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BPH

HMW keratin staining may show gaps in basal layer but will always be at least partial

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BPH

Like normal prostate tissue, nucleoli are not typically identified

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BPH

Branching glands, corpora amylacea, no nucleoli

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BPH

Nodule of glandular hyperplasia Theorized to respond better to finasteride

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BPH

Nodule of glandular hyperplasia Theorized to respond better to finasteride

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BPH

Nodule of glandular hyperplasia Glands can be dilated with secretions

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BPH

Nodule of glandular hyperplasia Glands can be dilated with secretions

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Polypoid Hyperplasia

Aka Prostatic urethral polyps; Present with hematuria Small polyps demonstrating typical prostatic-type epithelium; PSA and PAP positive; behavior is benign and recurrence after TUR is unusual. Histology can also be adenomatoid (nephrogenic adenoma; frequent recurrence) and adenomatous (endometroid)

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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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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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Acute Prostatitis

Inflammatory infiltrate within gland lumens

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Chronic Prostatitis

Inflammatory infiltrate surrounds the glands, involving the surrounding stroma

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Acute and Chronic Prostatitis

Infiltrate both in lumens and surrounding glands

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Malignant Lymphoma

Diffuse infiltration of parenchyma by small round blue cells with minimal cytoplasm Typically the normal architecture is spared Stains for leukocyte markers are positive

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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 severe dysplasia/ grade 3) High grade PIN is a marker for cancer Histologic features:
on low power, the glands appear large and complex, but more basophilic (blue) than the normal glands of BPH basal cells are present, if only focally high power shows prominent nucleoli, nuclear crowding and pseudostratification (piling up of the nuclei) also: the papillary structures at low power turn out to be caused by the cellular pile-up; in BPH, the papillary structures actuallly have fibrovascular cores and therefore are true papillae.

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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 a fibrovascular core

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Low Grade PIN

Multiple epithelial cell layers but unlike high grade 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 and rare punctate nucleoli. The cytoplasm is pale eosinophilic or clear

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Basal Cell Hyperplasia

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Basal Cell Hyperplasia

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Prostate Adenocarcinoma
Microscopic foci of cancer may begin in the 30s, present in 70% of men by the age of 70 80% occur in the peripheral zone, 10-20% in the transition zone; most appear yellow or gray-white grossly Histologic features:

Unlike other malignancies, neoplastic glands are very small, simple, and bland. Complexity in the prostate is generally a good sign, whereas small simple 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

Corpora amylacea

Elongated, refract light

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Prostate Cancer Blue Mucin

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Prostate Immunohistology

Alpha-methylacyl-CoA-racemase (racemase) aka, P504S, is an enzyme involved in beta-oxidation of branched chain fatty acids. Moderate to strong staining is seen in prostate cancer and high-grade PIN, but not in benign prostatic tissue. HMW cytokeratin antibody (34-E12) stains the cytoplasm of basal cells of the prostate. Increasing grades of PIN are associated with progressive disruption of the basal cell layer. Cancer cells consistently fail to react with this antibody. p63 antibody stains the nucleus of basal cells. Basal cell cocktail (34 -E12 and p63) increases the sensitivity of the basal cell detection and reduces staining variability, thus rendering basal cell immunostaining more consistent. PSA, PAP antibodies are useful in cases of unknown primary or very de-differentiated tumors.

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Prostate Immunohistology

HMW keratin and p63 stain basal cell layer of atrophic benign 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 so really a rank from 3-5 Prostatic cancers are typically heterogenous therefore receive the sum of their two most common 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 Gleason score, 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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Grade Grades 4: Fused 1-3 consist glands of small, (no stroma simple separating round glands some

of the withglands) a single or cell multiple layer surrounded lumens in a by single stroma gland. Grade 1: longer Glands attempting in nodular pattern Grade 5: No to create glands; cells Grade 2: Glands in vaguely rounded configuration in sheets, rows, or individual. Gradeclumps, 3: Glands infiltrating between normal glands

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Gleason Grading
Do

not try to assign a grade to treated tissue

Hormone therapy Prior radiation therapy of any kind

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Gleason Grade 1

nodules of uniform, closely-packed malignant glands, nucleoli are relatively inconspicuous

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Gleason Grade 2

Nodular configuration but more loosely packed.

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Gleason Grade 2

Nodular configuration but more loosely packed.

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Gleason Grade 3

Tumor infiltrates in and among the nonneoplastic prostatic glands

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Gleason Grade 3

Tumor infiltrates in and among the nonneoplastic prostatic glands

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Gleason Grade 3

Tumor infiltrates in and among the nonneoplastic prostatic glands

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Gleason Grade 4

Fused glands without completely surrounding stroma, poorly formed or multiple lumens

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Gleason Grade 4

Fused glands without completely surrounding stroma, poorly formed or multiple lumens

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Gleason Grade 4

Fused glands without completely surrounding stroma, poorly formed or multiple lumens

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Gleason Grade 4

Fused glands without completely surrounding stroma, poorly formed or multiple lumens

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Hypernephroid Gleason Grade 4

Abundant clear cytoplasm with a dot-like nucleus

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Mucinous Gleason Grade 4

Extracellular mucin makes up at least 25% of tumor volume

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Gleason Grade 5

Minimal gland formation, cells in sheets, clumps, cords

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Gleason Grade 5

May need PSA stain to confirm diagnosis

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Gleason Grade 5

Minimal gland formation, cells in sheets, clumps, cords

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Gleason Grade 5

Minimal gland formation, cells in sheets, clumps, cords

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Gleason Grade 5

Signet Ring Histology

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Cribriform

Smoothly-circumscribed nodules with large ducts that are filled and distended with tumor in a cribriform pattern can be called grade 3 or 4. The presence of central necrosis in a cribriform carcinoma raises the grade to 5.

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Gleason Grade 5

Grade 5 Cribiform with comedonecrosis

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Seminal Vesicle

Beware of trick questions!

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Seminal Vesicle

Look for golden-brown granules of lipofuscin pigment

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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 PSA levels may be only mildly elevated. Neuroendocrine stains positive

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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

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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

Rare in North America, more often in areas where Schistosomiasis is endemic Histologic features include keratin pearl formation, intercellular desmosomes, etc.

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Rhabdomyosarcoma

Average age 7 years, rapid growth Sheets of small round blue cells with scattered strap cells (tadpole cells) having cross-striations