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

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

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

Normal HMW keratin stains basal layer

BPH Occurs in Transition Zone Due to androgen stimulation & estrogen synergism

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

BPH Stromal Hyperplasia Theorized to respond better to alpha-blockade

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

BPH Basal Cell Layer not always easy to identify

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

BPH Like normal prostate tissue, nucleoli are not typically identified

BPH Branching glands, corpora amylacea, no nucleoli

BPH Nodule of glandular hyperplasia Theorized to respond better to finasteride

BPH Nodule of glandular hyperplasia Theorized to respond better to finasteride

BPH Nodule of glandular hyperplasia Glands can be dilated with secretions

BPH Nodule of glandular hyperplasia Glands can be dilated with secretions

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)

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

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

Acute Prostatitis Inflammatory infiltrate within gland lumens

Chronic Prostatitis Inflammatory infiltrate surrounds the glands, involving the surrounding stroma

Acute and Chronic Prostatitis Infiltrate both in lumens and surrounding glands

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

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.

PIN

PIN

Normal Gland and PIN

PIN

PIN Papillary lumenal projections have NO fibrovascular core

Compare to BPH Papillary structures each have a fibrovascular core

Low Grade PIN Multiple epithelial cell layers but unlike high grade PIN, has no nucleoli

High Grade PIN

High Grade PIN HMW keratin shows fragmented basal cell layer

Beware: Basal Cell Hyperplasia Nuclei are ovoid with finely reticular chromatin and rare punctate nucleoli. The cytoplasm is pale eosinophilic or clear

Basal Cell Hyperplasia

Basal Cell Hyperplasia

Prostate Adenocarcinoma Microscopic foci of cancer may begin in the 30’s, 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) Gleason’s grading system

Prostate Cancer Crystalloids Corpora amylacea Elongated, refract light

Prostate Cancer Blue Mucin

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 (34ß-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 ß-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.

Prostate Immunohistology HMW keratin and p63 stain basal cell layer of atrophic benign gland Racemase stains malignant cells

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.

Grade 4: “Fused” glands (no stroma separating some of the glands) or multiple lumens in a single gland. Grade 5: No longer attempting to create glands; cells in sheets, clumps, rows, or individual. Grades 1-3 consist of small, simple round glands with 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

Gleason Grading Do not try to assign a grade to treated tissue Hormone therapy Prior radiation therapy of any kind

Gleason Grade 1 nodules of uniform, closely-packed malignant glands, nucleoli are relatively inconspicuous

Gleason Grade 2 Nodular configuration but more loosely packed.

Gleason Grade 2 Nodular configuration but more loosely packed.

Gleason Grade 3 Tumor infiltrates in and among the non-neoplastic prostatic glands

Gleason Grade 3 Tumor infiltrates in and among the non-neoplastic prostatic glands

Gleason Grade 3 Tumor infiltrates in and among the non-neoplastic prostatic glands

Gleason Grade 4 Fused glands without completely surrounding stroma, poorly formed or multiple lumens

Gleason Grade 4 Fused glands without completely surrounding stroma, poorly formed or multiple lumens

Gleason Grade 4 Fused glands without completely surrounding stroma, poorly formed or multiple lumens

Gleason Grade 4 Fused glands without completely surrounding stroma, poorly formed or multiple lumens

Hypernephroid Gleason Grade 4 Abundant clear cytoplasm with a dot-like nucleus

Mucinous Gleason Grade 4 Extracellular mucin makes up at least 25% of tumor volume

Gleason Grade 5 Minimal gland formation, cells in sheets, clumps, cords

Gleason Grade 5 May need PSA stain to confirm diagnosis

Gleason Grade 5 Minimal gland formation, cells in sheets, clumps, cords

Gleason Grade 5 Minimal gland formation, cells in sheets, clumps, cords

Gleason Grade 5 Signet Ring Histology

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.

Gleason Grade 5 Grade 5 Cribiform with comedonecrosis

Seminal Vesicle Beware of trick questions!

Seminal Vesicle Look for golden-brown granules of lipofuscin pigment

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

Endometroid Carcinoma Typically arises in area of urethra/prostatic utricle PSA and PAP positive Often grade 3 or 4 but 5 if has necrosis

Transitional Cell Carcinoma Typically involves large ducts More cytologic atypia than prostate cancer PSA negative

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

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