Male Genital System(Part-III)

Normal Prostate

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

• HMW keratin stains basal layer

PROSTATITIS

• May be ACUTE, caused by the same pathogens as those implicated in UTI; lot of neutrophilicinfiltrates

• May be CHRONIC, usually abacterial -There is no history, however, of recurrent urinary tract infection. Expressed prostatic secretions contain more than 10 leukocytes per high-power field, but bacterial cultures are uniformly negative.

• Or from recurrent or persistent acute infections ;lymphocytic infiltration

GRANULOMATOUS PROSTATITIS

• Can non-TB or TB-related• Nonspecific granulomatous prostatitis is

relatively common and represents a reaction to secretions from ruptured prostatic ducts and acini.

Benign Prostatic Hyperplasia(Nodular Hyperplasia)

• BPH is characterized by proliferation of bothstromal and epithelial elements, withresultant enlargement of the gland and insome cases, urinary obstruction.

• It is present in a significant number of men by the age of 40, and its frequency rises progressively with age, reaching 90% by the eighth decade of life.

Etiopathogenesis:– Androgen Related. Conversion of testosterone by enzyme

type 2 5∞-reductase to DHT (dihydrotestosterone). This enzyme is located entirely on the stromal cell whereby the stromal cell is responsible for androgen-dependent prostatic growth.

– DHT binds to androgen receptors both present on the stromal and epithelial cell; DHT serves as an indirect mitogen on prostate (stromal) cells. DHT will induce increase production of several growth factors which will increase no. of stromal cells

– DHT does not increase cellular epithelial proliferation but instead inhibits death of the epithelial cells

NOTES• Testosterone (T) diffuses into the prostate epithelial and stromal cell.

T can interact directly with the androgen (steroid) receptors bound to the promoter region of androgen regulated genes.

• In the stromal cell a majority of T is converted into dihydrotestosterone (DHT)—a much more potent androgen—which can act in an autocrine fashion in the stromal cell or in a paracrinefashion by diffusing into epithelial cells in close proximity.

• DHT produced peripherally, primarily in the skin and liver, can diffuse into the prostate from the circulation and act in a true endocrine fashion.

• In some cases the basal cell in the prostate may serve as a DHT production site, similar to the stromal cell. Autocrine and paracrinegrowth factors may also be involved in androgen-dependent processes within the prostate.

Morphology

– BPH virtually always occurs in the inner, transitional zoneof the prostate.

– weighing between 60 and 100 g

– The nodules may appear solid or contain cystic spaces, thelatter corresponding to dilated glandular elements.

– The urethra is usually compressed by the hyperplasticnodules, often to a narrow slit.

– Microscopically the hyperplastic nodules are composed ofvariable proportions of proliferating glandular elementsand fibromuscular stroma. The hyperplastic glands arelined by tall, columnar epithelial cells and a peripherallayer of flattened basal cells

Nodular prostatic hyperplasia.

Well-defined nodules compress the urethra into a slitlike lumen.

Nodular hyperplasia of the prostate.

Low-power photomicrograph demonstrates a well-demarcated noduleat the right of the field with a portion of urethra seen to the left.

Glandular hyperplasia, note ABSENCE of nucleoli.

TUMORS OF PROSTATE

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

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 indistinct nucleoli

High Grade PIN

TUFTED PATTERN

MICROPAPILLARY PATTERN

CRIBRIFORM PATTERN

FLAT PATTERN

High Grade PIN

• HMW keratin shows fragmented basal cell layer

LOW GRADE PIN HIGH GRADE PIN

Architecture Epithelial cell crowding and stratification, with irregular spacing.

More crowding & stratification, 4 pattern-tufting, cribriform, micropappilary & flat.

Nuclei slightly enlarged with variation in size

markedly enlarged

Chromatin Normal Increased density &clumping

Nucleoli Rarely prominent Frequently large &prominent, sometimesmultiple.

Basal cell layer Intact May show some disruption.

Basement membrane Intact Intact

CARCINOMA OF THE PROSTATE-ADENOCARCINOMA

• Adenocarcinoma of the prostate occurs mainlyin men older than 50 years of age.

• It is the most common form of cancer in men,accounting for 25% of cancer in men in theUnited States in 2009.

• It is almost always occur in peripheral zone ofthe prostate.

Prostatic carcinoma with lots of nucleoli. Presence of nucleoli distinguishes this from BPH.

Etiology• Androgens play an important role in prostate

cancer the growth and survival of the cancer cells depend on the androgens

• The androgens bind to the androgen receptors and induce the expression of pro-growth and pro-survival genes.

Morphology

• Carcinoma of the Prostate– Most carcinomas detected clinically are not visible grossly. More

advanced lesions appear as firm, gray-white lesions with ill-defined margins that infiltrate the adjacent gland.

– On histologic examination, most lesions are moderatelydifferentiated adenocarcinomas that produce well-definedglands.

– The glands typically are smaller than benign glands and are linedby a single uniform layer of cuboidal or low columnar epithelium,lacking the basal cell layer seen in benign glands.

– In further contrast with benign glands, malignant glands arecrowded together and characteristically lack branching andpapillary infolding. The cytoplasm of the tumor cells ranges frompale-clear (as in benign glands) to a distinctive amphophilic (darkpurple) appearance. Nuclei are enlarged and often contain one ormore prominent nucleoli

Adenocarcinoma of the prostate.

Carcinomatous tissue is seen on the posterior aspect (lower left). Note thesolid whiter tissue of cancer, in contrast with the spongy appearance of thebenign peripheral zone on the contralateral side.

Adenocarcinoma of the prostate demonstrating smallglands crowded in between larger benign glands

Metastatic osteoblastic prostatic carcinoma

• Within vertebral bodies

•Haematogenous spread

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.

• 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

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.

OTHERS CARCINOMASmall 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

• 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

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.

• HMW keratin and p63 stain basal cell layer of atrophic benign gland

• Racemase stains malignant cells

THANK YOU….