Stanford School of Medicine

Surgical Pathology Criteria

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Prostatic Adenocarcinoma


  • Malignant epithelial neoplasm of the prostatic acini and ducts

See Classification/Links in left sidebar for Ductal, Intraductal, Small Cell, Mucinous types

Diagnostic Criteria

  • Presence of any one of the following features, even if only focal, is considered diagnostic of prostatic adenocarcinoma (none are required for diagnosis and in real life, it is rather uncommon to have these without obvious carcinoma near by)
    • Circumferential perineural invasion
      • Glands adjacent to and indenting nerves is not sufficient as a solitary diagnostic criterion
        • Partial surrounding of nerve may be  used as supportive evidence for a diagnosis of carcinoma
    • Glomeruloid formations
      • Epithelial proliferation projecting into the gland lumen
        • Typically a cribriform tuft with a single attachment to the side of the gland
        • Resembles a glomerulus in Bowman’s space
    • Mucinous fibroplasia / collagenous micronodules
      • Dense nodules of collagen surrounded and encased  by epithelium
        • Frequently entraps epithelial cells
      • Frequently appears to represent organized, hyalinized mucin
  • The presence of the following features can also be used to make the diagnosis of carcinoma, but none are specific by themselves and none of them is required
    • Generally more than one must be present and the focus must not be explainable as a benign glandular collection
    • Nuclear enlargement (moderate) and hyperchromasia large nucleoli
      • Nuclei are frequently enlarged, but typically uniform
        • Very large or pleomorphic nuclei suggest a non-prostatic primary (or normal seminal vesicle)
      • May be seen in acute inflammation, partial atrophy
    • Prominent enlarged nucleoli
      • Nucleoli >3 μ are very rare outside of carcinoma
        • Enlarged nucleoli but <3 μ, while not diagnostic may still be helpful
      • Basal cells have prominent but small nucleoli
    • Luminal blue (acidic) mucin or dense pink amorphous secretion
      • May be seen in adenosis and rarely in partial atrophy
    • Luminal crystalloids
      • Bright red, sharp corners, rectangular
      • May be seen in adenosis
      • Do not confuse with fractured corpora amylacea which may have occasional sharp edges
    • Sharp luminal border
      • Normal glands frequently have an undulating border
    • Nuclei consistently lined up basally
      • Normal glands usually have nuclei at many levels
    • Amphophilic cytoplasm
      • Not seen in all carcinomas but helpful when present
    • Infiltrative pattern
      • A distinct population of glands surrounding or separating benign glands
      • Lack of lobularity
      • Crowded, haphazard glands
  • Immunohistochemical demonstration of complete absence of basal cells can be confirmatory of a diagnosis of carcinoma but must be interpreted with caution (see Supplemental Studies)
  • See also:

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Last update 2/2/16

Atypical Small Acinar Proliferation

  • A descriptive term, it is not an entity
    • Term should be restricted to lesions that are probably carcinoma but either lack definitive diagnostic features or are too small to be certain that they do not represent the edge of a benign lesion
    • It should not be used if the lesion is benign but just unusual looking
  • For small foci, immunohistochemistry is primarily useful to disprove cancer, not to prove cancer
    • Basal cells must not be present on  immunohistochemistry
      • Racemase/AMACR staining may be helpful as an adjunct but its interpretation should always be secondary to that of the basal cell markers
    • Always decide before staining which glands you consider to make up the suspicious population and which are adjacent or surrounded normal glands
      • Detection of even rare basal cells in any of the glands of the suspicious population excludes carcinoma for the entire population
    • Absence of basal cells in a small focus of atypical glands does not prove carcinoma
      • Small negative foci may simply be a manifestation of sampling of a population of glands with variable/decreased numbers of basal cells
      • Absence of basal cells throughout a large, well sampled population with other features of carcinoma can be considered diagnostic
  • A diagnosis of ASAP will generally lead to repeat biopsies for a definitive diagnosis, if clinically appropriate (if other cores negative)
    • It is not justification for prostatectomy
  • Some usdful scenarios (see Epstein 2014 for more discussion)
    • Already some Gleason 4 on other core(s)
      • Don't pursue a focus that might be 3+3
      • Do pursue a focus that might be 3+4 (unless several cores already have some 4)
    • Focal 3+3 already identified or no cancer on other cores
      • Do pursue foci of 3+3 or 4
    • Extrensive 3+3 already identified
      • Don't pursue a focus that might be 3+3
      • Do pursue a focus that might be 3+4
    • Basically, if it isn't going to make a difference clinically, just call it ASAP

Supplemental Studies


  • Immunohistochemistry is primarily used in prostate pathology in three situations:
    • Identification of a differentiated, gland forming metastasis as prostatic in origin
      • Prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) are very sensitive and specific in this context
        • Virtually all untreated gland forming prostatic adenocarcinomas are positive for PSA and PAP
          • Either one is generally sufficient
          • Hormone treatment may lead to a negative result
        • Reactivity with other carcinomas is quite limited
          • PSA and PAP can stain salivary gland and breast neoplasms
          • PSA can stain cystitis glandularis and bladder adenocarcinoma
          • PAP stains rectal carcinoids
            • PSA is negative
            • Synaptophysin and chromogranin frequently stain rare to scattered cells in prostate carcinoma
          • Backup equivocal cases with NKX3.1
      • The choice of the complementary marker depends upon the context
        • TTF1 (lung) may stain small cell carcinoma of the prostate but is otherwise negative
        • CDX2 (GI tract) may react with a subset of prostate adenocarcinoma
          • Usually focal and weak but may be strong (including non-mucinous carcinomas)
        • GATA3 is sensitive (90%) and specific (also reacts with TCC)
          • BRST2 (GCDFP15) stains 60% of breast carcinoma and may stain nearly half of prostate adenocarcinomas
      • CK7 and 20 are of use only if they can exclude a carcinoma of another site
        • For example, a CK7 negative result is strongly against lung adenocarcinoma
        • Staining of prostate carcinomas is not very helpful as they may express a variety of CK phenotypes, most often CK7-20-
      • Racemase/AMACR is not useful in this situation
        • It is present in carcinomas of many types and sites
    • Distinction of very high grade prostatic adenocarcinoma from high grade urothelial carcinoma
      • NKX3.1 (nuclear) is most sensitive for prostate and quite specific
        • PSA and PAP may miss some (20%?) of very high grade or treated carcinomas
        • All three may be needed
        • Other backup p53 (cytoplasmic),
      • GATA3, p63 and/or high molecular weight cytokeratins are useful complementary markers
        • Nearly 90% of TCC are positive
        • Only extremely rare prostate adenocarcinomas are reactive
    • Distinction of benign from malignant prostate
      • p63 and high molecular weight cytokeratins (34BE12, CK5/6) are effective markers for basal cells
        • The presence of even one basal cell in a population may be sufficient to rule out carcinoma
        • The complete absence of basal cells is difficult to prove, but if the sample is large enough, it can be confirmatory of carcinomas
        • Note - a subset of atrophic carcinomas express p63 in the malignant cells (Giannico)
          • HMW keratin is negative
          • Recoginzed by infiltrative pattern, poorly formed glands, stratified, often spindled nuclei
            • Appear to do well clinically and should not be Gleason graded
      • Racemase/AMACR is a useful marker for carcinoma in the prostate
        • It is expressed in most carcinomas and is absent in most benign acini and ducts
          • It is not specific enough for use as a sole marker
            • Adenosis and partial atrophy may be positive
            • Partial staining and weak to moderate staining may be seen in other benign lesions
        • It is useful in cocktails that include basal cell markers
          • The racemase can highlight populations of acini for close examination for the presence of basal cells
        • Remember that it is not a marker of prostate origin in metastatic disease
      • See atypical small acinar proliferation for further discussion of the approach to small foci

Genetic Study

  • None currrently in use for diagnostic or therapeutic purposes

Differential Diagnosis

Benign lesions and patterns that may be confused with prostatic adenocarcinoma

  • Partial Atrophy
    • Retention of moderately abundant pale/clear cytoplasm lateral to the nuclei may produce pale glands that lack the blue appearance of atrophy
Partial Atrophy Carcinoma
Frequently merges with atrophic glands Distinct population from adjacent benign glands
Apical cytoplasm typically lost with preservation of lateral cytoplasm, separating the nuclei Apical cytoplasm typically preserved or increased while lateral is lost resulting in nuclear crowding
Bland nuclei, lacking enlarged nucleoli Large atypical nuclei with large nucleoli frequently present
Lacks infiltrative pattern Infiltrative pattern usually present
Basal cell markers positive, but may be decreased No basal cells
Non-straightforward cases should be resolved with IPOX stains for  basal cell markers

  • Post-atrophic Hyperplasia
    • Tightly packed very small cytologically bland glands
      • Glands look blue at low power because of scant cytoplasm
    • Usually near or around a larger duct
Post-atrophic Hyperplasia Carcinoma
Usually related to a large duct Haphazard infiltrative pattern
Bland nuclei Large atypical nuclei with large nucleoli usually present
Basal cell markers strongly positive Basal cells absent
Stroma typically sclerotic No sclerosis of stroma
Non-straightforward cases should be resolved with IPOX stains for cell markers

  • Basal Cell Hyperplasia
    • Usually fills many small glands
      • May appear infiltrative
    • Involved glands look blue from crowded nuclei with scant cytoplasm
Basal Cell Hyperplasia Carcinoma
Smooth borders, lobular pattern Infiltrative pattern
Usually produces a pattern of small blue glands with scant cytoplasm Low grade carcinomas are rarely blue in appearance as most have a moderate amount of pale or amphophilic apical cytoplasm
Residual luminal secretory population may be focally identified as a distinct population Carcinoma cells are typically uniform
Bland nuclei Large atypical nuclei usually present
Nucleoli are easy to find but are small to moderate size Nucleoli may be quite large
Basal cell markers strongly positive Basal cells absent
Non-straightforward cases should be resolved with IPOX stains for basal cell markers

  • Clear Cell Cribriform Hyperplasia
    • Big cribriform nodules of clear cells, generally rather obviously hyperplastic in spite of the cribriform pattern
Clear Cell Cribriform Hyperplasia Carcinoma
Smooth borders, lobular pattern Infiltrative pattern
Uniform, bland nuclei without prominent nucleoli Large atypical nuclei usually present
Nucleoli inconspicuous or absent Nucleoli may be quite large
May be associated with cellular BPH-type stroma Lacks BPH type-stroma or reactive stroma
Basal cell markers positive Basal cells absent
Non-straightforward cases should be resolved with IPOX stains for basal cell markers

  • Adenosis (Atypical Adenomatous Hyperplasia)
    • A benign lesion of no significance other than it simulates carcinoma
    • Occurs only in the transitional zone
      • Only rarely presents in a needle biopsy
      • Primarily seen in TURP and prostatectomy specimens
    • Well circumscribed tightly packed, largely uniform glands
      • This is not a diagnosis for a small group of suspicious glands (see ASAP)
      • May be sharply circumscribed over only part of the nodule
      • Small uniform glands frequently merge with larger glands with the same nuclear and cytoplasmic features
    • Some features suggestive of carcinoma may be seen;
      • Prominent nucleoli seen in 40% of cases, but not the macronucleoli (>3 μ) seen in many carcinomas
      • Crystalloids seen in about 40% of cases
      • Acidic luminal mucin seen in 2% of cases
    • Principal differential diagnosis is Gleason grade 2 carcinoma
      • Distinction requires IPOX stain for basal cells
        • Basal cells may be decreased in Adenosis
          • Demonstration of any basal cells in the population indicates adenosis in this context
          • Carcinoma must lack basal cells completely
      • With the advent of IPOX stains, we rarely diagnose Gleason grade 2 carcinoma and never grade 1 carcinoma; most are adenosis

  • Sclerosing Adenosis
    • Dense spindled stroma containing compressed, distorted epithelial elements
      • Entrapped epithelium ranges from small acini to cords and single cells
      • Basal cells present with unique immunologic profile
        • Usual markers positive (p63, HMWCK)
        • Also express myoepithelial markers (smooth muscle actin, S100)
Sclerosing Adenosis Carcinoma
Prominent sclerotic stroma Typically no stromal response in prostate
Basal cell markers strongly positive (p63, HMWCK) Basal cells absent
Myoepithelial markers positive in basal cells (smooth muscle actin, S100) Basal cells absent
Lacks cytologic atypia and macronucleoli May have cytologic atypia inclucing macronucleoli
Non-straightforward cases should be resolved with IPOX stains for basal cell and myoepithelial markers

  • Nephrogenic Adenoma
    • Periurethral (and bladder/ureter) and may involve adjacent prostate
      • Infrequent in needle biopsies but may appear in TURPs.
    • Tubulocystic and papillary patterns usually combined
      • Lined by a single layer of cells, frequently hobnailed
      • May cause diagnostic problems if tubular pattern predominates
    • Nephrogenic adenoma lacks HMW keratin/P63 positive basal cells and is racemase positive and may express prostatic acid phosphatase
Nephrogenic Adenoma Carcinoma
Papillary and cystic patterns usually also present Papillae and dilated cystic areas uncommon in low grade carcinoma
Prominent peritubular basement membrane Lacks basement membrane
PAX8, CK7 positive PAX8, CK7 negative
Non-straightforward cases should be resolved with IPOX stains

  • Seminal Vesicle and Ejaculatory Duct
    • Nuclear pleomorphism and complex architecture may falsely suggest malignancy
    • (Prostatic adenocarcinoma involving the seminal vesicles can be seen on needle biopsy and should be reported)
Seminal Vesicle / Ejaculatory Duct Carcinoma
Marked nuclear pleomorphism Marked nuclear pleomorphism is unusual in prostate carcinoma
Indistinct smudged chromatin Chromatin and nucleoli usually distinct
Cytoplasmic lipofuscin nearly always present Lipofuscin rarely seen in carcinoma
May have nuclear pseudoinclusions Nuclear pseudoinclusions rare
Surrounding muscular wall with a large central luminal space may identifiable in some biopsies Lacks a defined muscular wall and large central luminal space
Basal cell markers positive, prostate markers negative Basal cells absent, prostate markers positive
Non-straightforward cases should be resolved with IPOX stains for prostate and basal cell markers

    • Cowper gland
      • Periurethral, near apex
    Cowper Gland Prostatic Adenocarcinoma
    Lobular architecture with central ducts Infiltrative pattern
    Mucin filled cytoplasm, PASd+ Mucinous cytoplasm unusual
    No nuclear atypia or prominent nucleoli Atypical nuclei, frequently large nucleoli
    Basal cells markers positive, frequently smooth muscle actin positive No basal cells
    PAP negative (PSA may be positive) PAP and PSA positive
    Non-straightforward cases should be resolved with IPOX stains for prostate and basal cell markers


    Carcinoma patterns that may be confused with benign prostate

    • Pseudohyperplastic Carcinoma
      • Large glands with abundant eosinophilic cytoplasm, may be confused with hyperplasia
      • Branching papillae
      • Infiltrative pattern may be missing or difficult to appreciate
    Pseudohyperplastic Carcinoma (Benign) Hyperplasia
    Nuclei line up at base Nuclei frequently scattered at all levels
    Luminal border sharp and smooth usually at least in areas Luminal border undulating
    Lacks lobular pattern Lobular grouping
    Luminal crystalloids or blue mucin very suggestive if present Crystalloids and blue mucin absent
    Large atypical nuclei with large nucleoli Bland nuclei
    No basal cells Basal cell markers positive
    Glands may be densely packed with minimal stroma between Stroma clearly seen between glands
    Non-straightforward cases should be resolved with IPOX stains for basal cell markers

    • Foamy Gland Carcinoma
      • Voluminous xanthomatous cytoplasm
        • Usually has sharp luminal border
        • May virtually fill gland lumens
        • Mucin and lipid stains negative
      • Bland, pyknotic nuclei
        • Usually basal nuclei but may be located in center of cell
      • Common as a minor component of usual carcinoma
      • No difference in staining pattern from usual acinar carcinoma
    Foamy Gland Carcinoma (Benign) Hyperplasia
    Usually mixed with usual patterns of carcinoma Usually associated with benign glands and ducts
    Luminal border sharp and smooth Luminal border undulating
    Lacks lobular pattern Lobular grouping
    No basal cells Basal cell markers positive
    Non-straightforward cases should be resolved with IPOX stains for basal cell markers

    • Atrophic Carcinoma
      • Refers to a pre-therapy pattern
        • Radiation can also result in an atrophic pattern
      • Very little cytoplasm
        • Simulates small atrophic glands
        • If glands are dilated, see Microcystic Carcinoma
      • A subset of atrophic carcinomas express p63 in the malignant cells (Giannico)
        • HMW keratin is negative
        • Recoginzed by infiltrative pattern, poorly formed glands, stratified, often spindled nuclei
          • Appear to do well clinically and should not be Gleason graded
    Atrophic Carcinoma Benign Atrophy
    Infiltrative architecture, too many glands Lobular groups, frequently with an associated larger duct
    Most glands have round contours Most glands irregular and angulated
    Luminal crystalloids or blue mucin very suggestive if present Crystalloids and blue mucin absent
    Large atypical nuclei with large nucleoli but may be compressed by cellular flattening Bland nuclei
    No basal cells Basal cell markers positive, but may be decreased
    Non-straightforward cases should be resolved with IPOX stains for basal cell markers

    • Microcystic Carcinoma
      • Densely packed dilated/cystic glands
        • Glands approximately 10x the size of usual acinar carcinoma
    Microcystic Carcinoma Benign Ducts
    Crowded grouping dilated/cystic glands, frequently associated with typical carcinoma Scattered large ducts usually associated with small benign acini
    Luminal border sharp and smooth Luminal border undulating
    Nuclei line up at base Nuclei frequently scattered at all levels
    Luminal crystalloids and blue mucin very suggestive if present Crystalloids and blue mucin absent
    No basal cells Basal cell markers positive
    Non-straightforward cases should be resolved with IPOX stains for basal cell markers

    • PIN-like and Stratified Carcinoma
      • Mimics high grade PIN but lacks basal cells
        • May be flat, tufted or micropapillary
      • Some may be only two cells deep, simulating normal ducts
    PIN-like Carcinoma High Grade PIN
    Crowded grouping of large ducts/glands HG-PIN involves scattered large ducts separated by benign parenchyma
    No basal cells Basal cell markers positive
    May surround nerves No perineural invasion
    Non-straightforward cases should be resolved with IPOX stains for basal cell markers


    Cribriform prostatic lesions

    • Basal cell hyperplasia
      • Cribriform areas usually contain a distinct luminal secretory cell population
      • Associated with adjacent small acini plugged with small blue cells
        • Only grade 5 carcinoma could be composed of cells with such scant cytoplasm
      • Microcalcifications are frequent
        • They are rare in prostatic adenocarcinoma
      • Basal cell markers (p63 & HMWCK) are extensively positive
    • Clear cell cribriform hyperplasia
      • Lobular architecture
        • No infiltration
      • Uniform, bland nuclei without prominent nucleoli
      • May be associated with cellular BPH-type stroma
      • Basal cells present on IPOX stains
    • High grade PIN
      • Cribriform HG PIN is rare
      • Scattered large ducts involved
        • Ducts retain near normal caliber
      • Basal cells present on IPOX stains but may be decreased
      • Nuclei must be atypical but lack the marked pleomorphism of intraductal carcinoma (see below)
      • Frequently racemase positive
    • (Gleason pattern 3 carcinoma)
      • General consensus is that all or nearly all cases of cribriform pattern 3 carcinoma are really examples of something else on this list
    • Gleason pattern 4 carcinoma
      • Usually bordered by or associated with raggedly infiltrating glands or poorly formed glands
      • Cytologically atypical nuclei and nucleoli
    • Gleason pattern 5 carcinoma
      • As for Gleason pattern 4 but with comedonecrosis
      • Frequently non-cribriform pattern 5 is also present
    • Ductal carcinoma
      • Frequently papillary as well as cribriform
        • Cribriform spaces may be slit-like
      • Cytologically markedly atypical nuclei
      • Marked enlargement of duct size with irregular shapes and fusion
      • Cells may be columnar with pseudostratified, elongated nuclei
      • Graded as pattern 4 or 5, depending upon presence of comedonecrosis
        • Frequently associated with a pattern 3 component
      • Basal cells absent or rare
        • If present, it could be considered Intraductal Carcinoma
    • Intraductal carcinoma
      • Marked enlargement of duct size
        • May be irregular and branching
      • Ducts filled with cribriform, papillary and/or solid growth without fibrovascular stroma required
      • Basal cells present at least focally around periphery required
      • High grade cytology, comedonecrosis or solid/dense cribriform pattern required
        • High grade cytology means nuclei 6 times larger than normal
        • Dense cribriform means spaces make up <50% of intraluminal mass
        • Pleomorphic cells may preferentially localize to the periphery of nests
      • This is considered to represent high grade carcinoma that has invaded pre-existing ducts


    • The 2014 ISUP coonsensus proposal is to group Gleason patterns as defined below iinto clinically important groups
      • Group 1
        • Gleason score ≤6 (3+3 and below)
      • Group 2
        • Gleason 3+4=7
      • Group 3
        • Gleason 4+3=7
      • Group 4
        • Gleason score 8 (4+4, 3+5 or 5+3)
      • Group 5
        • Gleason scores 9 and 10
      • We report both Group and Gleason Score
    • The Gleason grading system is intended to be applied primarily at low power
      • Don’t go down on high power looking for one or two fused glands
      • Should be visible at 100x (10x objective)
    • The Score is the sum of the two most prevalent patterns subject to the following:
      • For needle biopsies
        • The predominant pattern is given first
        • The second most predominant pattern is given second, e.g. Gleason score 3+4 as long as the second score applies to >5% of the carcinoma
        • If the tertiary pattern is higher than both of the first two, it becomes the second pattern, regardless of its prevalence, e.g. 3+4 with tertiary 5 becomes 3+5
      • For prostatectomies
        • As for needle biopsies except that a high tertiary pattern is reported simply as a tertiary pattern e.g. Gleason score 3+4 with tertiary 5
    • Gleason grading criteria (based on 2005 ISUP modified system) (Epstein 2005, Egevad 2012)
      • Pattern 1
        • Circumscribed nodule of closely packed uniform glands
        • Described only in transition zone
        • Most if not all cases of Gleason 1+1 are really adenosis
        • We do not make this diagnosis, even as a secondary pattern
      • Pattern 2
        • Circumscribed nodule of loosely packed slightly variable glands
        • Described only in transition zone
        • Many/most cases of Gleason 2+2 are really adenosis
          • The entire lesion must be examined
          • IPOX for basal cells must be completely negative
        • We do not make the diagnosis of 2+2 or 2+3 on needle biopsies
          • Transition zone is rarely sampled and the entire lesion is rarely encompassed by the core
          • If the lesion is considered to be carcinoma it should be graded at least 3+3
      • Pattern 3
        • Single glands of variable size and density, with an infiltrative pattern, each separated by at least a strand of stroma
        • Critical distinctions from higher grade carcinomas are the widespread presence of well formed lumens and the lack of fused glands
        • This is the common pattern of low grade carcinoma
          • If no higher grade pattern is present, diagnose as Gleason 3+3
            • Resist the urge to imagine a component of pattern 2, even if the focus is small
        • Classical Gleason grading included sharply circumscribed cribriform in pattern 3
          • We consider this pattern 4, or in some cases high grade PIN
      • Pattern 4
        • Ragged infiltration with poorly formed glands or sheets and cords of fused glands
          • Poorly formed glands includes small nests of cells with only a rudimentary formed lumenal space (almost rosette like)
            • Intracytoplasmic lumens do not count as pattern 3, they are 4 or 5
          • Fused glands are recognized as back to back glands without intervening stroma
            • May produce a cribriform pattern
        • Glomeruloid bodies are pattern 4 by definition
        • Clear cell hypernephroid is pattern 4 by definition
      • Pattern 5
        • Ragged infiltrative single cells, cords or sheets without gland formation, small solid cylinders or any pattern with comedonecrosis
          • Occasional cells with these features can be seen in pattern 4, especially peripherally
          • Comedonecrosis should be unequivocal
        • Signet ring carcinoma is by definition pattern 5
    • Special considerations for grading
      • The proper score for a very small focus that is just barely diagnostic of carcinoma is 3+3=6, not 2+2 or 3+2
      • Even very small foci should get two patterns to avoid confusion (single number in a report may appear to be a sum of two patterns)
      • The most critical clinical distinctions occur with the recognition of pattern 4
        • Some urologists want to know what percentage of the cancer is pattern 4, if yours do, then report it
        • A recent large study suggests that carcinomas of Gleason 3+3 or lower do not have the ability to metastasize to nodes (Ross 2012)
      • Scores should be given for each individual core, if they are received separately labeled
      • Mucinous carcinoma should be graded bassed on the underoying pattern (usully it isi 4)
      • Treated carcinoma cannot be graded
        • If treated with radiation, we typically report that it cannot be graded but that it shows features of Gleason pattern 3 or 4 etc. if possible
          • Hormonally treated carcinoma cannot be graded at all
      • The rare variant of p63 positive adenocarcinoma should not be graded (Giannico)


    • Needle biopsy considerations
      • Record length of core involved by carcinoma and total length of core, in mm or give percent
        • If foci are discontinuous, include the intervening normal tissue in the measurement (Schultz 2013, Arias-Stella 2015)
      • Presence of carcinoma at the level of fat is diagnostic of extraprostatic extension
        • Skeletal muscle may be seen in normal prostate and is not useful
      • Perineural invasion indicates 95% probability of extraprostatic extension
        • It should be reported for needle biopsy specimens
      • Invasion of seminal vesicle – must rule out identical appearing ejaculatory ducts based on stated site of biopsy
    • Transurethral resection considerations
      • Evaluation of volume of carcinoma
        • Stage T1a:  5% or fewer of chips involved, all grade 3 or lower
          • (Counting chips is more practical than measuring area)
        • Stage T1b:  over 5% of chips involved or presence of any grade 4 or 5
        • Entirely submit first 15 gm, then 1 cassette for each additional 5 grams up to 30 gm total, then 1 cassette for each additional 10 gm
    • Prostatectomy considerations
      • Evaluate for extraprostatic extension (EPE)
        • Infiltration of fat is diagnostic of EPE
          • Most commonly seen in posterior prostate
        • Anterior periprostatic tissue has no fat
          • Evaluation for EPE requires recognition of the contour of the limit of the normal prostatic glands
          • The prostate should be differentially inked and sections taken in a manner that permits localization of the section
        • EPE cannot be assessed in the apex as the capsule is very indistinct there
        • Skeletal muscle is present in the apex and anterior prostate associated with normal glands and is not useful for assessing EPE
        • Involvement of the base of the prostate is not EPE
        • True seminal vesicle involvement requires invasion of wall, not just adventitia.
      • Evaluation of margin is completely independent of EPE assessment
        • Differential inking permits localization of positive margins
      • The apex and base should each be amputated and sectioned perpendicularly to the surface
      • Reporting of perineural involvement is not required for prostatectomies
      • Multiple foci of carcinoma, if bilateral, are staged as pT2c (Andreolu 2010)
        • Most truly multifocal carcinomas represent distinct clones
          • Staged as bilateral involvement anyway


    Prostatic Carcinomas

    Prostatic Benign Lesions/Patterns Simulating Carcinoma

    Other Lesions


    • The entire January 2012 issue of Histopathology is devoted to reviews on prostate cancers:
      • Epstein, J. I. (2012), Diagnosis of limited adenocarcinoma of the prostate. Histopathology, 60: 28–40.
      • Montironi, R., Scarpelli, M., Mazzucchelli, R., Cheng, L. and Lopez-Beltran, A. (2012), The spectrum of morphology in non-neoplastic prostate including cancer mimics. Histopathology, 60: 41–58.
      • Humphrey, P. A. (2012), Histological variants of prostatic carcinoma and their significance. Histopathology, 60: 59–74.
      • Delahunt, B., Miller, R. J., Srigley, J. R., Evans, A. J. and Samaratunga, H. (2012), Gleason grading: past, present and future. Histopathology, 60: 75–86.
      • Cheng, L., Montironi, R., Bostwick, D. G., Lopez-Beltran, A. and Berney, D. M. (2012), Staging of prostate cancer. Histopathology, 60: 87–117.
      • Egevad, L. (2012), Handling of radical prostatectomy specimens. Histopathology, 60: 118–124.
      • Kristiansen, G. (2012), Diagnostic and prognostic molecular biomarkers for prostate cancer. Histopathology, 60: 125–141.
    • Two recent reviews in Archives of Pathology:
      • Brian Robinson, Cristina Magi-Galluzzi, Ming Zhou , (2012) Intraductal Carcinoma of the Prostate. Archives of Pathology & Laboratory Medicine: April 2012, Vol. 136, No. 4, pp. 418-425.
      • Lars Egevad, Roberta Mazzucchelli, Rodolfo Montironi , (2012) Implications of the International Society of Urological Pathology Modified Gleason Grading System. Archives of Pathology & Laboratory Medicine: April 2012, Vol. 136, No. 4, pp. 426-434.
    • Eble JN, Sauter G, Epstein JI, Sesterhenn IA (Eds): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press. Lyon 2004.
    • Kaleem Z, Swanson PE, Vollmer RT, Humphrey PA. Prostatic adenocarcinoma with atrophic features: a study of 202 consecutive completely embedded radical prostatectomy specimens. Am J Clin Pathol. 1998 Jun;109(6):695-703.
    • Egan AJ, Lopez-Beltran A, Bostwick DG. Prostatic adenocarcinoma with atrophic features: malignancy mimicking a benign process. Am J Surg Pathol. 1997 Aug;21(8):931-5.
    • Cina SJ, Epstein JI. Adenocarcinoma of the prostate with atrophic features. Am J Surg Pathol. 1997 Mar;21(3):289-95.
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    • Levi AW, Epstein JI. Pseudohyperplastic prostatic adenocarcinoma on needle biopsy and simple prostatectomy. Am J Surg Pathol. 2000 Aug;24(8):1039-46.
    • Arista-Nasr J, Martinez-Benitez B, Valdes S, Hernández M, Bornstein-Quevedo L.
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    • Yaskiv O, Cao D, Humphrey PA. Microcystic adenocarcinoma of the prostate: a variant of pseudohyperplastic and atrophic patterns. Am J Surg Pathol. 2010 Apr;34(4):556-61.
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    • Tran TT, Sengupta E, Yang XJ. Prostatic foamy gland carcinoma with aggressive behavior: clinicopathologic, immunohistochemical, and ultrastructural analysis. Am J Surg Pathol. 2001 May;25(5):618-23.
    • Nelson RS, Epstein JI. Prostatic carcinoma with abundant xanthomatous cytoplasm. Foamy gland carcinoma. Am J Surg Pathol. 1996 Apr;20(4):419-26.
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    • Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Grading Committee. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005 Sep;29(9):1228-42.
    • Guo CC, Epstein JI. Intraductal carcinoma of the prostate on needle biopsy: Histologic features and clinical significance. Mod Pathol. 2006 Dec;19(12):1528-35.
    • Herawi M, Epstein JI. Immunohistochemical antibody cocktail staining (p63/HMWCK/AMACR) of ductal adenocarcinoma and Gleason pattern 4 cribriform and noncribriform acinar adenocarcinomas of the prostate. Am J Surg Pathol. 2007 Jun;31(6):889-94.
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    • Brinker DA, Potter SR, Epstein JI. Ductal adenocarcinoma of the prostate diagnosed on needle biopsy: correlation with clinical and radical prostatectomy findings and progression. Am J Surg Pathol. 1999 Dec;23(12):1471-9.
    • Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI. Do adenocarcinomas of the prostate with Gleason score (GS) ≤6 have the potential to metastasize to lymph nodes? Am J Surg Pathol. 2012 Sep;36(9):1346-52.
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    • Bostwick DG; Wollan P; Adlakha K. Collagenous micronodules in prostate cancer. A specific but infrequent diagnostic finding. Archives of Pathology and Laboratory Medicine, 1995 May, 119(5):444-7
    • Giannico GA, Ross HM, Lotan T, Epstein JI. Aberrant expression of p63 in adenocarcinoma of the prostate: a radical prostatectomy study. Am J Surg Pathol. 2013 Sep;37(9):1401-6.
    • Warrick JI, Humphrey PA. Foamy gland carcinoma of the prostate in needle biopsy: incidence, Gleason grade, and comparative α-methylacyl-CoA racemase vs. ERG expression. Am J Surg Pathol. 2013 Nov;37(11):1709-14.
    • Schultz L, Maluf CE, da Silva RC, Falashi Rde H, da Costa MV, Schultz MI. Discontinuous foci of cancer in a single core of prostatic biopsy: when it occurs and performance of quantification methods in a private-practice setting. Am J Surg Pathol. 2013 Dec;37(12):1831-6. PubMed PMID: 24225844.
    • Epstein JI, Egevad L, Humphrey PA, Montironi R; Members of the ISUP Immunohistochemistry in Diagnostic Urologic Pathology Group. Best practices recommendations in the application of immunohistochemistry in the prostate: report from the international society of urologic pathology consensus conference. Am J Surg Pathol. 2014 Aug;38(8):e6-e19. PubMed PMID: 25029122.
    • Mohanty SK, Smith SC, Chang E, Luthringer DJ, Gown AM, Aron M, Amin MB. sEvaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas. Am J Clin Pathol. 2014 Aug;142(2):173-83. PubMed PMID: 25015857.
    • Andreoiu M, Cheng L. Multifocal prostate cancer: biologic, prognostic, and therapeutic implications. Hum Pathol. 2010 Jun;41(6):781-93. PubMed PMID: 20466122.
    • Arias-Stella JA 3rd, Varma KR, Montoya-Cerrillo D, Gupta NS, Williamson SR. Does discontinuous involvement of a prostatic needle biopsy core by adenocarcinoma correlate with a large tumor focus at radical prostatectomy? Am J Surg Pathol. 2015 Feb;39(2):281-6. doi: 10.1097. PubMed PMID: 25353288
    • Amin MB, Lin DW, Gore JL, Srigley JR, Samaratunga H, Egevad L, Rubin M, Nacey J, Carter HB, Klotz L, Sandler H, Zietman AL, Holden S, Montironi R, Humphrey PA, Evans AJ, Epstein JI, Delahunt B, McKenney JK, Berney D, Wheeler TM, Chinnaiyan AM, True L, Knudsen B, Hammond ME. The critical role of the pathologist in determining eligibility for active surveillance as a management option in patients with prostate cancer: consensus statement with recommendations supported by the College of American Pathologists, International Society of Urological Pathology, Association of Directors of Anatomic and Surgical Pathology, the New Zealand Society of Pathologists, and the Prostate Cancer Foundation. Arch Pathol Lab Med. 2014 Oct;138(10):1387-405. doi: 10.5858/arpa.2014-0219-SA. Epub 2014 Aug 5. Review. PubMed PMID: 25092589.
    • Montironi R, Hammond EH, Lin DW, Gore JL, Srigley JR, Samaratunga H, Egevad L, Rubin MA, Nacey J, Klotz L, Sandler H, Zietman AL, Holden S, Humphrey PA, Evans AJ, Delahunt B, McKenney JK, Berney D, Wheeler TM, Chinnaiyan A, True L, Knudsen B, Epstein JI, Amin MB; College of American Pathologists; International Society of Urological Pathology; Association of Directors of Anatomic and Surgical Pathology. Consensus statement with recommendations on active surveillance inclusion criteria and definition of progression in men with localized prostate cancer: the critical role of the pathologist. Virchows Arch. 2014 Dec;465(6):623-8. doi: 10.1007/s00428-014-1668-5. Epub 2014 Oct 16. PubMed PMID: 25316188.
    • Epstein JI(1), Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA; Grading
      Committe. The 2014 International Society of Urological Pathology (ISUP) Consensus
      Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading
      Patterns and Proposal for a New Grading System. Am J Surg Pathol. 2016 Feb;40(2):244-52. doi: 10.1097/PAS.0000000000000530..
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