Prostatic carcinoma
Adenocarcinoma of peripheral ducts and acini

Author: Kenneth Iczkowski, M.D. (see Authors page)

Revised: 10 August 2016, last major update August 2016

Copyright: (c) 2003-2016,, Inc.

PubMed Search: Prostatic Adenocarcinoma of Peripheral Ducts and Acini

Definition / General
Tumor distribution:
  • 95% of prostate cancer is acinar type (Figs. 1-4) and 5% is ductal type
  • 70% arises from peripheral zone (posterior and lateral)
  • Often spares transition (periurethral/anterior) zone (TZ); TZ involvement is usually due to tumor expansion from the peripheral zone
  • At radical prostatectomy, > 90% have posterior tumor but only 65% have tumor anteriorly
  • Anterior tumor is associated with higher tumor volume and margin positivity (BJU Int 2006 Dec;98:1167), although outcomes are similar to posterior tumors (Prostate Cancer Prostatic Dis 2014 Mar;17:75)
  • Tumor in biopsy is clinically “significant” if Gleason score ≥3+4 and tumor length ≥ 3 mm; in prostatectomy specimens, it is significant if tumor volume ≥ 0.5 cc, or the stage is ≥ pT3a (Curr Opin Urol 2014 May;24:209).

Tumor extension:
  • Extraprostatic extension (EPE) is most common, and is defined as tumor in contact with extraprostatic fat
  • The prostate has a fibromuscular pseudocapsule that is discontinuous at its apex, bladder base and anteriorly, so the “capsule” is not relevant in staging prostate cancer
  • Local invasion occurs via seminal vesicles (if tumor infiltrates muscular wall) and bladder base; rarely via prostatic urethra
  • Rectal invasion is rare due to tough Denonvillier’s fascia which abuts pseudocapsule; 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, 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:
  • In cystoprostatectomy specimens for bladder cancer, most studies describe a 50% rate of incidental prostatic adenocarcinoma; 20% were clinically significant (Fig 2) (Am J Clin Pathol 2009 Feb;131:279)
Urinary cytology:
  • Not used since 1980s; largely replaced by automated spring loaded 18 gauge biopsy
  • Not useful for screening because difficult to identify well differentiated tumors with cytology, easier for poor/moderately differentiated tumors

Core biopsy (see also separate topic):
Transurethral resection:
  • Presence of tumor indicates either extensive spread by conventional carcinoma or central carcinoma
  • Humphrey et al. recommend complete sampling for patients younger than age 60 years (Humphrey: Prostate Pathology, 2003, page 40)
  • For patients over age 60, random sampling of 8 blocks (Hum Pathol 2007 Sep;38:1305) or 10 blocks (Humphrey book) can be performed; if cancer is detected, then complete submission is warranted.
  • If only high grade PIN is found, embed all tissue and obtain deeper levels

Frozen section diagnosis:
  • Look for architectural disarray or perineural invasion
  • Lymph node frozen section/imprints: 10% false negatives
Prognostic Factors

Recurrence after radical prostatectomy:
  • Median interval 40 months
  • Mean tumor size 3.2 mm
  • Often lacks 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)
  • Radical prostatectomy (not warranted if positive pelvic nodes), brachytherapy (radioactive seeds), targeted focal cryotherapy, external beam radiation therapy, watchful waiting (for low grade tumors, localized tumor or limited life expectancy), chemotherapy or hormonal therapy (LHRH analogs, antiandrogens, orchiectomy).
  • Most tumors are androgen sensitive
  • Use PSA to monitor tumor response
Gross Description
  • Gritty and firm, gray-yellow, poorly delimited, more easily felt than seen
  • Accurate identification of prostate cancer by gross inspection is possible in only 63% of cases, with a 19% false positive rate (Am J Clin Pathol 1998;110:38)
Gross Images
Images hosted on PathOut server, contributed by Dr. Iczkowski:

Readily recognizable cancer in anterior horn of peripheral zone.
Grossly, cancer is not always so obvious

Micro Description
  • Pattern depends on Gleason grade
  • Small glands, sometimes medium to large glands, papillary or cribriform glands or solid growth, single cells or 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)
  • 75% of high grade PIN may abuts carcinoma (Hum Pathol 2014 Jan;45:54)
  • Mitotic figures extremely rare except in high grade tumors
  • Malignant transformation is accompanied by loss of basal cells, first reported by Totten in 1953 (AMA Arch Pathol 1953;55:131)
  • Glands are “too many, too small, too crowded” (need not be clustered)
  • Most common pattern is infiltrative, small to medium sized glands (Gleason 3) - detect on low power as closely packed glands with irregular outline, smooth luminal surface, splitting stromal fibers (Figs. 5-8)
  • Large gland pattern also occurs and resembles atrophy (Fig. 1)
  • Less common, usually in transition zone or central zone, is a Gleason 2 pattern of small sized glands forming expansive nodules on low power, regular round glands, small size, usually not multifocal.
  • Assignment of Gleason 1 is discouraged in all instances and assignment of Gleason 2 is discouraged in biopsies (see Grading).
  • Cribriform pattern may appear intraductal with preserved basal cell layer, but is usually invasive and if so should be graded as Gleason 4 (Am J Clin Pathol 2011 Jul;136:98)
  • Single cell infiltration (Gleason 5 pattern) may resemble lobular carcinoma of breast
  • Ancillary findings in adenocarcinoma: perineural invasion, glomerulation, mucinous fibroplasia (collagenous micronodules, Fig. 9); rarely,perineural invasion is the only diagnostic feature of malignancy (Arch Pathol Lab Med 2000;124:98)
  • Features favoring but not diagnostic of adenocarcinoma: small glands between larger glands, crowded glands that stand out from adjacent benign glands, prominent nucleoli in at least 10% of cells, nuclear enlargement, hyperchromatic nuclei, luminal blue mucin, amphophilic cytoplasm, mitotic figures, crystalloids, adjacent high grade PIN (Arch Pathol Lab Med 2000;124:98)
  • Features associated with false positive diagnoses: atrophic cytoplasm, atypical glands associated with inflammation, small crowded glands merging with larger benign glands (adenosis), distinctive features in Central Zone (Hum Pathol 2002;33:518), high grade PIN, small atypical crowded glands adjacent to high grade PIN (may be tangential sectioning of PIN)
  • Note: As discussed in later sections, the diagnosis of ASAP (atypical small acinar proliferation suspicious for cancer) may apply if strict cancer criteria are not met

Angiolymphatic invasion
  • Not commonly seen

  • More common in benign than malignant prostate, but present in Gleason pattern 5 with comedo-type necrosis (dystrophic calcification), 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)

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)

  • 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

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)

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)
Micro Images
Adenocarcinoma - Image hosted on PathOut server, contributed by Dr. Iczkowski:

Fig. 1 Pseudoatrophic pattern
of prostate cancer

Adenocarcinoma - Images hosted on other servers:

Fig. 2 Incidental prostatic
adenocarcinoma in

Fig. 3 Metastases
to male papillary
breast cancer


Fig. 4 Metastases of prostatic adenocarcinoma:


Fig. 5 Small crowded glands with simplified architecture; round or oval lumens

Fig. 6 Abnormal architecture


Fig. 7 Prominent nucleoli

Fig. 8 All essential histologic features present


Fig. 9 Collagenous micronodules surround cancer glands

Various images, contributed by Dr. Semir Vranić,
Clinical Center of the University of Sarajevo (Bosnia and Herzegovina)

Cellularity of vessels - Images hosted on other servers:

Increased media cellularity
of native vessels -
various images

Crystalloids - Image hosted on other servers:

In benign glands

Mucin - Images hosted on other servers:

Acidic mucin

Perineural invasion (PNI) - Images hosted on other servers:

Perineural invasion

Cluster of malignant glands
surrounds two nerve twigs

Minimal prostate cancer - Images hosted on other servers:

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)