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Prostatic carcinoma

Adenocarcinoma of peripheral ducts and acini

Reviewers: Monika Roychowdhury, M.D., (see Reviewers page)
Revised: 14 May 2014, last major update July 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.


Tumor distribution:
● 70% arise from peripheral zone (posterior, lateral, anterior)
● Usually spares periurethral zone except in late stages
● Radical prostatectomy specimens usually have tumor posteriorly (>90%) and anteriorly (65%)
● Anterior tumor associated with higher tumor volume and extraprostatic extension (Am J Clin Pathol 1999;112:373)

Tumor extension:
● Local invasion occurs via seminal vesicles (if infiltrates muscular wall) and bladder base, rarely via prostatic urethra
● Rectal invasion rare due to tough Denonvillier’s fascia; may present as anterior rectal mass, stricture or serosal implants
● Seminal vesicle invasion occurs via (a) direct spread along ejaculatory duct complex, (b) spread outside prostate, through capsule, then into seminal vesicle, (c) isolated deposits of cancer in seminal vesicle with no contiguous primary cancer in the prostate (Am J Surg Pathol 1993;17:1252)

Incidentally detected:
● Considered clinically significant if total tumor volume 0.5 cc or more; Gleason grade 4 or 5; extraprostatic extension; seminal vesicle invasion; lymph node metastasis present; positive surgical margins
● In cystoprostatectomy specimens for bladder cancer, incidental prostatic adenocarcinoma in 50%, 20% were clinically significant (Am J Clin Pathol 2009;131:279)


● Usually skeletal system, lung/pleura, liver, adrenals and lymph nodes; also testes
● Breast if estrogen therapy (may metastasize to male papillary breast cancer)
● Dural metastases at autopsy (Arch Pathol Lab Med 2001;125:880)
● Autopsy study: 35% had metastases, most common sites were bone (90%), lung (46%), liver (25%), pleura (21%), adrenals (13%)
● Spine involvement common even in small tumors
● Tends to be upward spread from lumbar to cervical level (Hum Pathol 2000;31:578)
● Markers of prostatic origin include PSA, PAP, NKX3.1 (Am J Surg Pathol 2010;34:1097)
Bony metastases: multiple, usually osteoblastic not osteolytic, may radiographically simulate Paget’s disease or osteosarcoma; usually lumbar spine, sacrum or pelvis due to tumor spread via Batson’s vertebral venous plexus; histology shows clusters of malignant glands surrounded by new bone formation; PSA/PAP+ even after decalcification; may cause hypocalcemia, hypophosphatemia, increased alkaline phosphatase
Lung metastases: small acinar or cribriform growth, frequent lymphangitic permeation, no stromal response, uniform round nuclei with prominent nucleoli, intraluminal blue mucin, prominent cell borders; may have carcinoid-like architectural features but no fine chromatin pattern (Am J Clin Pathol 2002;117:552); may resemble bronchogenic carcinoma (Am J Clin Pathol 1990;94:641); usually PSA/PAP+
Nodal metastases: pelvic chains, then retroperitoneum; rarely skips pelvis and goes to lungs/liver; overwhelmingly associated with high grade, high stage and large volume disease (Am J Surg Pathol 2010;34:1862); latent prostate cancers detected at autopsy almost never have nodal metastases; poorly differentiated carcinomas may metastasize to left supraclavicular or mediastinal nodes (detect with PSA/PAP); 30-40% occur contralateral to dominant tumor; rarely occurs with anterior dominant tumors

Recurrence after radical prostatectomy

● Median interval 40 months
● Mean tumor size 3.2 mm
● Often lack overt histologic features of malignancy, but need lower threshold for diagnosis because atypical prostate glands should not be present at all (Am J Surg Pathol 2002;26:431)

Prognostic factors

● Stage, Gleason score (not useful if minimal tumor, Am J Surg Pathol 2000;24:1634), surgical margins, preoperative PSA, perineurial invasion
● Angiolymphatic invasion (Am J Surg Pathol 2000;24:859)
● Size of nodal metastasis (Am J Surg Pathol 1998;22:1491)
● Recent study: poor prognosis if Gleason score > 6, PSA > 40 ng/mL, stage B2 or higher, Caucasian (Rev Saude Publica 2010;44:344)
● Patients < age 20: carcinoma rare, usually have obstructive symptoms, advanced stage, high grade, poor response to treatment, survival < 1 year


Urinary cytology:
● Difficult to identify well differentiated tumors; easier for poor/moderately differentiated tumors; not useful for screening since 10% false negatives; largely replaced by automated spring-loaded 18 gauge biopsy

Core biopsy (see separate topics also):
● High grade prostatic vs. high grade urothelial carcinoma: prostatic adenocarcinoma has oval nuclei with smooth borders; fine, powdery, evenly distributed chromatin; large nucleolus (if present), no significant pleomorphism (Am J Clin Pathol 2000;113:29); note that normal seminal vesicle cells are atypical and resemble carcinoma but are MUC6+ (Am J Surg Pathol 2003;27:519)

● Presence of tumor indicates either extensive spread by conventional carcinoma or central carcinoma
● Sampling: 5 blocks/12 grams will detect 90% of carcinomas; 8 blocks detects 98% of carcinomas
● If <5% carcinoma (T1a/stage A1), sample more chips (T1b/stage A2 if > 5%)
● If high grade PIN only, embed all tissue and obtain deeper levels

Frozen section diagnosis:
● Look for architectural disarray or perineurial invasion
● Lymph node frozen section/imprints: 10% false negatives


● Radical prostatectomy (not warranted if positive pelvic nodes), brachytherapy (radioactive seeds), external beam radiation therapy, watchful waiting (for low grade tumors, localized tumor or limited life expectancy), chemotherapy or hormonal therapy (LHRH analogs, antiandrogens, orchiectomy) for metastastic disease
● Most tumors are androgen sensitive, at least initially
● Use PSA to monitor tumor response

Gross description

● Gritty and firm, gray-yellow, poorly delimited, more easily felt than seen
● Often undetectable if tumor small

Gross images

Various images

Micro description

● Pattern depends on Gleason grade
● Small glands, medium-sized glands, cribriform glands or diffuse single cell infiltration with necrosis
● Cytoplasm usually finely granular, may be clear/foamy due to intracellular lipid
● Nuclear enlargement, hyperchromasia, prominent nucleoli (>3 microns is specific for malignancy, >1 micron is suggestive)
● High grade PIN present in 80% of carcinomas
● Mitotic figures extremely rare except in high grade tumors
● Malignant transformation is accompanied by loss of basal cells, first reported by Totten in 1953
● Glands are “too many, too small, too crowded” (need not be clustered)
● Most common pattern is infiltrative medium sized glands (Gleason 3) - detect on low power as closely packed glands with irregular outline, smooth inner surface, scanty stroma
● Less common, usually in transition zone or central zone is a Gleason 1 or 2 pattern of small sized glands forming expansive nodules on low power, regular round glands, small size, usually not multifocal
● Cribriform pattern may appear intraductal with preserved basal cell layer, but is usually invasive (Gleason 3 if smooth borders, Gleason 4 if uneven borders)
● Single cell infiltration (Gleason 5 pattern) may resemble lobular carcinoma of breast
Features diagnostic of adenocarcinoma: perineural invasion, glomerulation, mucinous fibroplasia (collagenous micronodules); perineural invasion may be only diagnostic feature of malignancy (Am J Surg Pathol 1999;23:918)
Features favoring but not diagnostic of adenocarcinoma: small glands between larger glands, crowded glands that stand out from adjacent benign glands, prominent nucleoli, nuclear enlargement, hyperchromatic nuclei, amphophilic cytoplasm, mitotic figures, blue luminal mucin, pink luminal mucin, crystalloids, adjacent high grade PIN
Features associated with false positive diagnoses: atrophic cytoplasm, atypical glands associated with inflammation, small crowded glands merging with larger benign glands (adenosis), small crowded glands with corpora amylacea (adenosis), high grade PIN, small atypical crowded glands adjacent to high grade PIN (may be tangential sectioning of PIN)
Note: only diagnose if stringent criteria met, otherwise classify as “focus of small atypical glands suspicious for malignancy”

Micro images

Small crowded glands with simplified architecture; round or oval lumens

Small atypical glands infiltrating in between larger benign glands

Abnormal architecture

Numerous small glands with simplified round or oval lumens

Prominent nucleoli

Small crowded glands lined by single layer of cells, nuclear enlargement and hyperchromasia, prominent nucleoli and intraluminal blue mucin

Incidental prostatic adenocarcinoma in cytoprostatectomy specimen for bladder cancer

Metastases of prostatic adenocarcinoma: H&E, PSA, PAP, NKX3.1

Metastases to male papillary breast cancer

Recurrence after radical prostatectomy - various images

Collagenous micronodules


Angiolymphatic invasion


● Not commonly seen



● More common in benign than malignant prostate, but present in Gleason pattern 5 with comedo-type necrosis (dystrophic calcification) and within lumina of Gleason pattern 3 cribriform and small acinar types and within collagenous micronodules (Arch Pathol Lab Med 1998;122:152)

Cellularity of vessels


● In radical prostatectomy specimens, increased vessel cellularity may be associated with higher grade tumors (Mod Pathol 2000;13:717)

Micro images

Increased media cellularity of native vessels - various images

Corpora amylacea


● Don’t confuse with crystalloids
● Benign but may be found in tumor
● May arise from release of prostate secretory granules
● Remnants condense to form eosinophilic bodies, which adsorb and layer onto surface of prostatic corpora amylacea, causing them to enlarge (Hum Pathol 2000;31:94)



● Resemble Bence-Jones crystals (Ig kappa/lambda)
● Seen in lumina of 10-23% of carcinomas, usually Gleason 3
● Rarely in benign glands or metastatic foci (Am J Clin Pathol 1994;101:266)
● Composed of inorganic sulfur
● Deeply eosinophilic, rhomboid
● In benign specimens, not a significant risk factor for subsequent diagnosis of cancer (Am J Surg Pathol 1998;22:446, Am J Surg Pathol 1997;21:725)
● Same sulfur content as prostate secretory granules and corpora amylacea (Hum Pathol 2000;31:94)

Micro images

In benign glands



● Acidic mucin found in lumina in 2/3
● Looks basophilic or deeply eosinophilic, confirm with Alcian blue or colloidal iron stains
● Normal prostate secretes neutral mucins, although acid mucins also seen in adenosis and post-radiation therapy

Micro images

Acidic mucin

Perineural invasion (PNI)


● Common (85% of all tumors)
● When present in needle core biopsy, suggests extraprostatic extension (Am J Clin Pathol 1999;111:223), but see (Am J Surg Pathol 2003;27:432)
● Diameter of perineural invasion may be prognostic factor (Hum Pathol 2001;32:828)
● May mediate local tumor spread via tumor expression of nerve cell adhesion molecule (Hum Pathol 2003;34:457)
● Outdated theories are: (a) tumor spreads via perineurial lymphatics (they don’t exist); (b) perineurial space represents tissue plane of least resistance (Am J Surg Pathol 1980;4:143), but this doesn’t explain why morphologically similar tumors have varying neurotropism); (c) there is different nerve distribution in malignant vs. benign specimens (actually is similar, S100 not useful for identifying PNI, Am J Clin Pathol 2001;115:39)

Micro images

Perineural invasion

Cluster of malignant glands surrounds two nerve twigs

Prostatic secretory granules


● Identifiable with strong glutaraldehyde fixation
● 1 micron, brightly eosinophilic granules (PSA+, PAP+) that fill cytoplasm of secretory cells
● Reduced in carcinoma and high grade PIN (Hum Pathol 2000;31:1515)
● Formaldehyde causes granules to appear empty (Hum Pathol 1998;29:1488)

Minimal prostate cancer

Micro images

Various images

Six atypical glands

Left: Gleason pattern 3; right: alpha methylacyl-CoA racemase (AMACR) stain

8-10 atypical glands

Basal cell-specific markers (HMWCK, p63)

End of Prostate > Prostatic carcinoma > Adenocarcinoma of peripheral ducts and acini

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