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Updated Protocol for the Examination of Specimens From Patients With Carcinomas of the Prostate Gland.



A Basis for Checklists

This protocol is intended to assist pathologists in providing clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a specific patient or specimen.

It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathologists are urged to familiarize themselves with the document. Should a physician choose to deviate from the protocol based on the circumstances of a particular patient or specimen, the physician is advised to make a contemporaneous written notation of the reason for the procedure followed.

The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insurance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diagnostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, litigation An action brought in court to enforce a particular right. The act or process of bringing a lawsuit in and of itself; a judicial contest; any dispute.

When a person begins a civil lawsuit, the person enters into a process called litigation.
, or reimbursement purposes. The College cautions that any uses of the protocol for these purposes involve considerations that are beyond the scope of this document.

UPDATED PROTOCOL FOR THE EXAMINATION OF SPECIMENS FROM PATIENTS WITH CARCINOMAS OF THE PROSTATE GLAND

1. Needle Biopsy needle biopsy
n.
Removal of a specimen for biopsy by aspirating it through a needle or trocar that pierces the skin or the external surface of an organ and continues into the underlying tissue to be examined. Also called aspiration biopsy.
 

A. Clinical information

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information

a. Relevant history (eg, urinary obstruction)

b. Relevant findings (eg, digital rectal examination Digital rectal examination
A routine screening test that is used to detect any lumps in the prostate gland or any hardening or other abnormality of the prostate tissue.
, prostate-specific antigen prostate-specific antigen
n. Abbr. PSA
A protease secreted by the epithelial cells of the prostate gland. Serum levels are elevated in patients with benign prostatic hyperplasia and prostate cancer.
, ultrasound, magnetic resonance imaging magnetic resonance imaging (MRI), noninvasive diagnostic technique that uses nuclear magnetic resonance to produce cross-sectional images of organs and other internal body structures. )

c. Clinical diagnosis (eg, carcinoma)

d. Procedure (eg, thick-core [14-gauge] transrectal or transperineal biopsy, thin-core [18-gauge] image-guided gun biopsies [sextant sextant, instrument for measuring the altitude of the sun or another celestial body; such measurements can then be used to determine the observer's geographical position or for other navigational, surveying, or astronomical applications. , octant, etc])

e. Specific site of needle biopsy (eg, peripheral zone, transition zone, apex, base, etc)

B. Macroscopic macroscopic /mac·ro·scop·ic/ (mak?ro-skop´ik) gross (2).

mac·ro·scop·ic or mac·ro·scop·i·cal
adj.
1. Large enough to be perceived or examined by the unaided eye.

2.
 examination

1. Specimen

a. Number of pieces

b. Unfixed/fixed (specify fixative fixative /fix·a·tive/ (fik´sit-iv) an agent used in preserving a histological or pathological specimen so as to maintain the normal structure of its constituent elements.

fix·a·tive
adj.
)

c. Dimensions

d. Orientation, if designated by surgeon

e. Results of intraoperative consultation

2. Tissue submitted for microscopic examination (eg, all tissue), frozen section tissue fragment(s), unless saved for special studies

3. Special studies (specify) (eg, histochemistry histochemistry /his·to·chem·is·try/ (his?to-kem´is-tre) that branch of histology dealing with the identification of chemical components in cells and tissues.histochem´ical

his·to·chem·is·try
n.
, immunohistochemistry, morphometry mor·phom·e·try
n.
Measurement of the form of organisms or of their parts.



morpho·met
, DNA analysis DNA analysis Any technique used to analyze genes and DNA. See Chromosome walking, DNA fingerprinting, Footprinting, In situ hybridization, Jeffries' probe, Jumping libraries, PCR, RFLP analysis, Southern blot hybridization. , cytogenetic cytogenetic /cy·to·ge·net·ic/ (-je-net´ik)
1. pertaining to chromosomes.

2. pertaining to cytogenetics.


cytogenetic

pertaining to or originating from the origin and development of the cell.
 analysis)

C. Microscopic evaluation

1. Tumor

a. Histologic type (note A)

b. Gleason score Gleason score Oncology A value derived from the Gleason grading system which is the sum of the 2 most predominant histologic patterns seen in prostate CA  with primary and secondary grades (note B)

c. Quantitation of tumor (eg, proportion [%] of prostatic tissue involved by neoplasm neoplasm or tumor, tissue composed of cells that grow in an abnormal way. Normal tissue is growth-limited, i.e., cell reproduction is equal to cell death. ) (note C)

d. Local invasion (note D)

(1) Periprostatic fat

(2) Seminal vesicle seminal vesicle
n.
Either of a pair of pouchlike glands situated on each side of the male urinary bladder that secrete seminal fluid and nourish and promote the movement of spermatozoa through the urethra.
 

e. Perineural invasion perineural invasion Surgical pathology Extension of epithelial cells around nerves which, while typical of malignancy, may be seen in sclerosing adenosis–breast, and is not per se an indication of malignancy  (note E)

f. Blood/lymphatic vessel invasion

2. Additional pathologic findings, if present

a. High-grade prostatic intraepithelial neoplasia Prostatic intraepithelial neoplasia (PIN) is a non-invasive lesion in the prostate gland which is though to be a precursor to prostate cancer. Microscopically, PIN is a collection of irregular cells which are fully contained within the gland structure and have not spread to  (note F)

b. Therapy-related changes

c. Other

3. Results/status of special studies (specify)

4. Comments

a. Correlation with intraoperative consultation, as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate

II. Transurethral transurethral /trans·ure·thral/ (trans?u-re´thral) performed through the urethra.

transurethral

performed through the urethra.
 Prostatic Resection

A. Clinical information

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information

a. Relevant history (eg, urinary obstruction)

b. Relevant findings (eg, digital rectal examination, prostate-specific antigen, ultrasound, magnetic resonance imaging)

c. Clinical diagnosis (eg, carcinoma)

d. Operative procedure (transurethral resection of prostate transurethral resection of prostate TURP Urology The standard method for managing prostate disease–BPH and CA, in which a curette is inserted transurethrally and crescent-shaped 'chips' are removed Complications Higher rates of postoperative cystoscopy,  [TURP TURP transurethral resection of the prostate.

TURP
abbr.
transurethral resection of the prostate


Transurethral resection of the prostate (TURP) 
])

e. Operative findings

B. Macroscopic examination

1. Specimen

a. Organ(s)/tissues(s) included

b. Unfixed/fixed (specify fixative)

c. Weight

d. Descriptive features

e. Results of intraoperative consultation

2. Tissue submitted for microscopic examination (note G)

a. All grossly suspicious chips (note G)

b. Specimen [is less than or equal to] 12 g, submit entirely(*)

c. Specimen [is greater than] 12 g, submit at least 12 g (about 6-8 cassettes)(*)

d. Frozen section tissue fragment(s) (unless saved for special studies)

(*) Note: If an unsuspected carcinoma is found in tissue submitted and it involves [is less than or equal to] 5% of the tissue examined, all remaining tissue should be submitted for microscopic examination.

3. Special studies (specify)

C. Microscopic evaluation

1. Tumor

a. Histologic type (note A)

b. Gleason score with primary and secondary grades (note B)

c. Quantitation of tumor (note C)

d. Local invasion (note D)

(1) Periprostatic fat

(2) Seminal vesicle

e. Perineural invasion (note E)

f. Blood/lymphatic vessel invasion

2. Additional pathological findings, if present

a. Prostatic intraepithelial neoplasia (note F)

b. Atypical adenomatous hyperplasia Atypical adenomatous hyperplasia
The over-growth of the endometrium. This precancerous condition is estimated to progress to cancer in one third of the cases.

Mentioned in: Endometrial Cancer
 

c. Therapy-related changes

d. Other(s)

3. Results of special studies

4. Comments

a. Correlation with intraoperative consultation, as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate

III. Suprapubic or Retropubic Enucleation enucleation /enu·cle·a·tion/ (e-noo?kle-a´shun) removal of an organ or other mass intact from its supporting tissues, as of the eyeball from the orbit.
Enucleation
Surgical removal of the eyeball.
 (Subtotal subtotal /sub·to·tal/ (sub-to´t'l) less than, but often almost, complete.  Prostatectomy Prostatectomy Definition

Prostatectomy refers to the surgical removal of part of the prostate gland (transurethral resection, a procedure performed to relieve urinary symptoms caused by benign enlargement), or all of the prostate (radical prostatectomy,
)

A. Clinical information

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information

a. Relevant history (eg, urinary obstruction)

b. Relevant findings (eg, palpable mass, elevated prostate-specific antigen, imaging)

c. Clinical diagnosis

d. Procedure (eg, enucleation)

e. Operative findings

B. Macroscopic examination

1. Specimen

a. Tissue(s)/organ(s) received

b. Unfixed/fixed (specify fixative)

c. Size (3 dimensions)

d. Weight

e. Descriptive features (eg, necrosis, nodular nodular

marked with, or resembling, nodules.


nodular dermatofibrosis
see dermatofibrosis.

nodular episcleritis
see nodular fasciitis (below).

nodular fasciitis
a firm painless nodular swelling, 0.
 hyperplasia)

f. Orientation, if indicated by surgeon

g. Identification of margins

h. Results of intraoperative consultation

2. Tumor, if identified

a. Location(s)

b. Size(s)

c. Descriptive features

d. Extent of invasion (note H)

3. Blocks submitted for microscopic evaluation

a. Tumor or areas suspicious for tumor

b. Other representative blocks (approximately 8 cassettes)([dagger])

c. Frozen section tissue fragment(s) (unless saved for special studies)

([dagger]) Note: If an unsuspected carcinoma is found in tissue submitted and it involves 5% or less of the tissue examined, additional blocks should be submitted for microscopic analysis.

4. Special studies (specify)

C. Microscopic evaluation

1. Tumor

a. Histologic type (note A)

b. Gleason score with primary and secondary grades (note B)

c. Quantitation of tumor

(1) Size of tumor(s), 2 or more dimension(s)

(2) Proportion (%) of specimen involved by tumor

d. Location of tumor(s)

e. Local invasion (note H)

f. Perineural invasion (note E)

g. Blood/lymphatic vessel invasion

2. Margins

3. Additional pathologic findings, if present

a. High-grade prostatic intraepithelial neoplasia (note E)

b. Atypical adenomatous hyperplasia

c. Therapy-related changes

d. Other(s)

4. Results/status of special studies (specify)

5. Comments

a. Correlation with intraoperative consultation, as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate

IV. Radical Prostatectomy Radical prostatectomy
Surgical removal of the entire prostate, a common method of treating prostate cancer.

Mentioned in: Prostate Cancer

radical prostatectomy  
 

A. Clinical information

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

2. Responsible physician(s)

3. Date of procedure

4. Clinical information

a. Relevant history (previous diagnosis, treatment, includes prostate-specific antigen, imaging)

b. Relevant clinical findings

c. Procedure

(1) Perineal perineal /peri·ne·al/ (-ne´al) pertaining to the perineum.
Perineal
The diamond-shaped region of the body between the pubic arch and the anus.
 procedure

(2) Retropubic procedure

i. Nerve sparing

ii. Standard radical

d. Operative findings

e. Anatomic site(s) of specimen(s)

B. Macroscopic examination

1. Specimen

a. Organ(s)/tissues included

b. Unfixed/fixed (specify fixative)

c. Opened/unopened

d. Orientation, if indicated by surgeon

e. Structures included in specimen

(1) Prostate

(2) Seminal vesicles

(3) Segments of vasa deferentia

(4) Bladder neck Bladder neck
The place where the urethra and bladder join.

Mentioned in: Urinary Incontinence
 

(5) Urethra urethra (yrē`thrə), canal in most mammals that carries urine from the bladder to the outside of the body; in the male it also serves as a genital duct.  

(6) Other(s) (specify)

f. Size (3 dimensions)

g. Weight (prostate separately)

h. Obstruction of urethra (partial/complete)

i. Descriptive features (eg, necrosis, nodular hyperplasia)

j. Results of intraoperative consultation

2. Tumor(s), if identified

a. Location(s)

b. Size(s)

c. Descriptive features

d. Extent of local invasion

3. Regional lymph nodes Lymph nodes
Small, bean-shaped masses of tissue scattered along the lymphatic system that act as filters and immune monitors, removing fluids, bacteria, or cancer cells that travel through the lymph system.
 

a. Location

b. Number (each location, if possible)

4. Blocks submitted for microscopic evaluation (include diagrams, if appropriate) (note G)

a. Tumor(s) (each grossly recognizable tumor)

b. Blocks from other anatomic locations within the prostate (to evaluate for multicentricity)

c. Blocks to determine extent of invasion (note H)

(1) Prostatic capsule and periprostatic tissue adjacent to each tumor, including inked margins

(2) Seminal vesicles

(3) Periprostatic tissue at bases of seminal vesicles

d. Apex (note J)

e. Vesical vesical /ves·i·cal/ (ves´i-k'l) pertaining to the urinary bladder. Cf. cystic.

vesical

pertaining to or emanating from the urinary bladder.
 neck margin (note J)

f. All lymph nodes

g. Frozen section tissue fragment(s) (unless saved for special studies)

h. Other tissues (specify)

5. Special studies (specify) (eg, immunohistochemistry, ploidy analysis ploidy analysis Lab medicine A flow cytometry technique that evaluates a cell's chromosome content–a parameter of aggressiveness in CA; in general, diploidy–ie, the presence of 2 haploid sets of chromosomes, is a normal or near-normal state; in , S-phase fraction)

C. Microscopic evaluation

1. Tumor

a. Histologic type (note A)

b. Gleason score with primary and secondary grades (note B)

c. Location(s)

d. Extent of local invasion (note H)

(1) Extraprostatic extension

(2) Seminal vesicle involvement

2. Margins (location and extent of margins involved with tumor) (see note I)

3. Regional lymph nodes

a. Number (specify location)

b. Number involved by tumor

(1) Specify location, if possible

(2) Size of metastatic Metastatic
The term used to describe a secondary cancer, or one that has spread from one area of the body to another.

Mentioned in: Coagulation Disorders


metastatic

pertaining to or of the nature of a metastasis.
 deposit (eg, if [is less than] 2 mm = micrometastasis)

(3) Extracapsular extension, if present

4. Additional pathologic findings, if present

a. High-grade intraepithelial neoplasia intraepithelial neoplasia An in situ carcinoma confined to an epithelium that may superficially penetrate adnexal glands, measuring < either 3 mm or 5 mm depending on the criteria used; IN is adjectivally modified according to site of origin See CIN

 

b. Therapy-related changes

c. Other(s)

5. Metastasis metastasis /me·tas·ta·sis/ (me-tas´tah-sis) pl. metas´tases  
1. transfer of disease from one organ or part of the body to another not directly connected with it, due either to transfer of pathogenic microorganisms or to
 to other organ(s) or structure(s) (specify sites)

6. Other tissue(s)/organ(s)

7. Results/status of special studies (specify)

8. Comments

a. Correlation with intraoperative consultation, as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate

EXPLANATORY NOTES

A: Histologic Type.--This protocol applies only to carcinomas of the prostate gland. The Histologic Classification of Prostate Carcinoma is recommended as shown below.[1] However, this protocol does not preclude the use of other systems of classification or histologic types. Mixtures of different histologic types should be indicated.

Histologic Classification of Carcinoma of the Prostate Adenocarcinoma adenocarcinoma: see neoplasm.  (conventional, not otherwise specified) Special variants of adenocarcinoma and other carcinomas

Prostatic duct adenocarcinoma

Mucinous mucinous /mu·ci·nous/ (mu´si-nus) resembling, or marked by formation of, mucin.

mucinous

relating to, resembling or containing mucin.
 (colloid colloid (kŏl`oid) [Gr.,=gluelike], a mixture in which one substance is divided into minute particles (called colloidal particles) and dispersed throughout a second substance. ) adenocarcinoma

Signet ring cell signet ring cell A usually malignant cell containing copious clear cytoplasm that flattens a hyperchromatic nucleus to one side, having an appearance fancifully likened to a signet ring; CAs composed predominantly of SRCs often carry a worse prognosis; the  carcinoma

Adenosquamous carcinoma

Squamous cell carcinoma squamous cell carcinoma
n.
A carcinoma that arises from squamous epithelium and is the most common form of skin cancer. Also called cancroid, epidermoid carcinoma.
 

Basaloid and adenoid cystic carcinoma adenoid cystic carcinoma
n.
A carcinoma characterized by large epithelial masses containing round glandlike spaces or cysts, frequently containing mucus, that are bordered by layers of epithelial cells. Also called cylindromatous carcinoma.
 

Transitional cell carcinoma tran·si·tion·al cell carcinoma
n.
A malignant neoplasm derived from transitional epithelium and occurring primarily in the urinary bladder, ureters, or renal pelvises.


transitional cell carcinoma Bladder cancer, see there
 

Small cell carcinoma small cell carcinoma
n.
See oat cell carcinoma.


small cell carcinoma Small cell undifferentiated carcinoma, undifferentiated carcinoma A highly aggressive malignancy, usually of lung, which arises in proximal bronchi
 

Sarcomatoid carcinoma

Lymphoepithelioma-like carcinoma

Undifferentiated carcinoma, not otherwise specified

B: Gleason Score.--The Gleason grading system Gleason grading system
A method of predicting the tendency of a tumor in the prostate to metastasize based on how similar the tumor is to normal prostate tissue.
 is recommended for use in all prostatic cancer specimens.[2-6] The Gleason score is the sum of the primary (most predominant) Gleason grade and the secondary (second most predominant) Gleason grade. Where no secondary Gleason grade exists, the primary Gleason grade is doubled to arrive at a Gleason score. The primary and secondary grades should be reported in parentheses See parenthesis.

parentheses - See left parenthesis, right parenthesis.
 after the Gleason score, that is, Gleason score 7(3,4) or 7(3+4). In needle biopsy specimens in which more than 2 patterns are present and the worst grade is neither the predominant nor the secondary grade, the predominant and the highest grade should be chosen to arrive at a score (eg, 60% grade 3, 30% grade 2, 10% grade 4 is scored as 3 + 4 = 7). When multiple needle biopsy specimens are submitted and they have differing Gleason scores, an overall (composite) Gleason score for the case should be clearly reported in a note.

In radical prostatectomy specimens in which more than 1 separate tumor is identified, the Gleason scores of the individual tumors may be reported separately, or at the very least the Gleason score of the most significant lesion should be recorded. For instance, if there is a large Gleason score 5 transition zone cancer and a separate smaller Gleason score 7 peripheral zone cancer, both scores or at least the latter score should be reported rather than the scores being averaged.

Another grading system may be used according to institutional preference (eg, World Health Organization, M. D. Anderson), but the Gleason score must be included to facilitate comparison of data.
Gleason Grades (Patterns)

Grade 1   Single, separate, closely packed acini

Grade 2   Single acini, more loosely arranged, less uniform

Grade 3   Single acini of variable size, and separation,
          cribriform and papillary patterns

Grade 4   Irregular masses of acini and fused epithelium,
          can show clear cells

Grade 5   Anaplastic carcinoma

Gleason scores may be grouped into differentiation
(prognostic) categories:

2-4    Well differentiated
5-6    Moderately well differentiated
7      Moderately poorly differentiated
8-10   Poorly differentiated

or

2-6    Well differentiated
7      Moderately differentiated
8-10   Poorly differentiated


C: Quantitation of Tumor.--There are many methods of estimating the amount of tumor in prostatic specimens.[7-16] In core biopsies, the absolute number or percentage of cores involved, the linear extent of involvement in millimeters, and the proportion (percent) of surface area of prostatic tissue involved may be used. In transurethral resectates, the proportion (percent) of tissue involved by carcinoma and the number of positive chips (foci) may be used. In subtotal and radical prostatectomy specimens, the percentage of tissue involved by tumor can also be "eyeballed." Additionally, in these latter specimens it may be possible to measure a dominant tumor nodule nodule: see concretion.
nodule

In geology, a rounded mineral concretion that is distinct from, and may be separated from, the formation in which it occurs.
 in at least 2 dimensions and to indicate the number of blocks involved by tumor over the total number of prostatic blocks submitted.

For the purpose of this protocol it is recommended that at the very least, the proportion (percent) of prostatic tissue involved by tumor be included for all specimens.

D: Local Invasion in Needle Biopsies.--Occasionally in needle biopsies, periprostatic fat is present and involved by tumor.[7-9] This observation should be noted since it indicates that the tumor is at least stage pT3a. Furthermore, if seminal vesicle tissue is present (either unintentionally or intentionally as in a directed biopsy) and is involved by tumor, this should be reported since it indicates that the tumor is at least stage pT3b. Seminal vesicle invasion is defined by involvement of the muscular wall.[7-9,17] At times, especially in needle biopsy specimens, it is difficult to distinguish between seminal vesicle and ejaculatory e·jac·u·la·to·ry
adj.
Relating to an ejaculation.
 duct-type tissue. It is important not to overinterpret ejaculatory duct as seminal vesicle-type tissue. Ejaculatory duct epithelium is generally surrounded by loose fibrous connective tissue Fibrous connective tissue
Dense tissue found in various parts of the body containing very few living cells.

Mentioned in: Corneal Transplantation
 with abundant blood vessels, whereas the seminal vesicle epithelium is surrounded by smooth muscle bundles constituting its wall.

E: Perineural Invasion.--Perineural invasion on core needle biopsies has been associated with a high risk of extraprostatic extension in some studies, although the exact prognostic significance remains to be determined.[18-21] Perineural invasion has also been found to be an independent risk factor for predicting an adverse outcome in patients treated with external beam radiation.[18] The value of perineural invasion as an independent prognostic factor, however, has been questioned in a multivariate analysis.[22]

F: Prostatic Intraepithelial Neoplasia.--The diagnostic term prostatic intraepithelial neoplasia (PIN), unless qualified, refers to high-grade PIN.[23] Low-grade PIN is generally not reported. The presence of PIN should be reported in all biopsy specimens, including those with carcinoma.[9] High-grade PIN in a biopsy without evidence of carcinoma is a significant risk factor for the presence of carcinoma on subsequent biopsies.[24,25] The reporting of high-grade PIN in prostatectomy specimens is optional.

G: Submission of Tissue for Microscopic Evaluation in Transurethral Resection and Radical Prostatectomy Specimens.--Specimens weighing less than 12 g should be submitted in their entirety, usually in 6 to 8 cassettes.[26,27] For specimens greater than 12 g, the initial 12 g are submitted (6-8 cassettes), and 1 cassette for every additional 5 g may be submitted.

In general random chips are submitted; however, if some chips are firmer or have a yellow or orange-yellow appearance, they should be preferentially submitted.

In radical prostatectomy specimens with no grossly visible tumor, the specimen may be submitted in its entirety or partially sampled in a systematic fashion. One method of partial sampling involves submitting the entire apical apical /ap·i·cal/ (ap´i-k'l) pertaining to an apex.

a·pi·cal
adj.
1. Relating to the apex of a pyramidal or pointed structure.

2.
 segment and bladder neck along with alternating posterior transverse sections. Two or three random blocks demonstrating the anterior surface are also submitted along with samples of each seminal vesicle, including their juncture with prostate proper.

H: Extraprostatic Extension.--Extraprostatic extension is the preferred term for the presence of tumor beyond the confines of the prostate gland.[8,28] Tumor abutting on or admixed with fat constitutes extraprostatic extension. Extraprostatic extension may also be reported when tumor involves perineural spaces in the neurovascular bundles, even in the absence of periprostatic fat involvement. In certain locations, such as the anterior prostate and bladder neck regions, there is a paucity of fat, and in these locations extraprostatic extension is determined when the tumor extends beyond the confines of the normal glandular glandular /glan·du·lar/ (glan´du-ler)
1. pertaining to or of the nature of a gland.

2. glanular.


glan·du·lar
adj.
1.
 prostate. Sometimes there is a distinct bulging tumor nodule that may be associated with a desmoplastic stromal Stromal
A type of tissue that is associated with the support of an organ.

Mentioned in: Wilms' Tumor
 reaction.

I: Margins.--The entire surface of the prostate should be inked to evaluate the surgical margins.[29-36] Usually, surgical margins should be designated as "negative" if tumor is not present at the inked margin and as "positive" if tumor cells touch the ink at the margin. Positive surgical margins should not be interpreted as extraprostatic extension. If the surgical margin is positive, the pathologist should state this explicitly, although this finding is not relied on for pathologic staging. The specific locations of the positive margins should be documented, and there should be some indication (eg, number of positive blocks, linear extent in millimeters) of the extent of margin positivity.

J: Apex and Bladder Neck.--The apex should be closely examined because of its unusual susceptibility to positive margins.[29-31] At the apex, tumor admixed with skeletal muscle elements does not constitute extraprostatic extension. The apical and bladder neck surgical margins should be sectioned entirely, preferably with a perpendicular orientation. Microscopic involvement of bladder neck muscle fibers in radical prostatectomy specimens should not be equated with a pT4 designation. The latter generally requires gross involvement of the bladder neck.

K: TNM TNM tumor-nodes-metastasis; see under staging.

TNM

tumor, nodes and metastases; a system of cancer staging (see TNM staging).
 and Stage Groupings.--The protocol recommends the use of the TNM Staging System TNM staging system,
n.pr stands for tumor
node
metastasis, a recognized method used to identify and predict the course of disease of a patient diagnosed with cancer.
 for carcinoma of the prostate of the American Joint Committee on Cancer The American Joint Committee on Cancer (AJCC) is an organization best known for defining and popularizing cancer staging standards. External links
  • Official page
  • UCSF
  • Cancer.gov
 (AJCC AJCC American Joint Committee on Cancer ) and the International Union Against Cancer (UICC UICC Union International Contre le Cancer International Union against Cancer ) as shown below.[37,38]

By AJCC/UICC convention, the designation "T" of the TNM classification refers exclusively to the first resection of a primary tumor The prefix symbol "p" refers to the pathologic classification of the TNM (pTNM), as opposed to the clinical classification. Pathologic classification is based on gross and microscopic examination. Therefore, pT entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT category, pN entails removal of nodes adequate to validate lymph node metastasis, and pM implies microscopic examination of distant lesions. Clinical classification (cTNM) is usually carried out by the referring physician before treatment during initial evaluation of the patient or when pathologic classification is not possible.

The absence or presence of residual tumor following preoperative pre·op·er·a·tive
adj.
Preceding a surgical operation.



preoperative

preceding an operation.


preoperative care
the preparation of a patient before operation.
, nonsurgical therapy (eg, chemotherapy and/or radiation treatment) may be described by the symbol "R" and classified as follows:
RX   Residual tumor cannot be assessed
R0   No residual tumor
R1   Microscopic residual tumor
R2   Macroscopic residual tumor


If residual tumor is present, its extent may be documented by the TNM classification preceded by the symbol "y" (eg, ypT1).

Local recurrence following a previous resection should be classified as listed above with the prefix "r" (eg, rpT1).
Primary Tumor, Clinical (cT)

TX   Primary tumor cannot be assessed

T0   No evidence of primary tumor

T1   Clinically inapparent tumor not palpable or visible
     by imaging

     T1a   Tumor incidental histologic finding in 5% or
           less of tissue resected

     T1b   Tumor incidental histologic finding in more
           than 5% of tissue resected

     T1c   Tumor identified by needle biopsy (eg, because
           of elevated prostate-specific antigen)

T2   Tumor confined within the prostate(*)

     T2a   Tumor involves one lobe

     T2b   Tumor involves both lobes

T3   Tumor extends through the prostatic capsule([dagger])

     T3a   Extracapsular extension (unilateral or bilateral)

     T3b   Tumor invades the seminal vesicle(s)

T4   Tumor is fixed or invades adjacent structures other
     than the seminal vesicles, bladder neck, external
     sphincter, rectum, levator muscles, and/or pelvic
     wall


(*) Tumor found in one or both lobes by needle biopsy, but that is not palpable or visible by imaging, is classified as T1c.

([dagger]) Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2. Tumor extension into periprostatic soft tissue, as opposed to organ-confined cancer (T2), is classified as T3.
Primary Tumor, Pathologic (pT)

pT2(*)          Organ confined
                pT2a Unilateral
                pT2b Bilateral

pT3             Extraprostatic extension
                pT3a Extraprostatic extension
                pT3b Seminal vesicle extension

pT4([dagger])   Invasion of bladder, rectum


(*) There is no pathologic T1 category.

([dagger]) Invasion of bladder indicates direct spread into the wall of the urinary bladder. The basal prostatic stroma stroma /stro·ma/ (stro´mah) pl. stro´mata   [Gr.] the matrix or supporting tissue of an organ.stro´malstromat´ic

stro·ma
n. pl. stro·ma·ta
1.
 blends imperceptibly into the bladder neck musculature musculature /mus·cu·la·ture/ (mus´kul-ah-cher) the muscular apparatus of the body or of a part.

mus·cu·la·ture
n.
The arrangement of the muscles in a part or in the body as a whole.
, and in most instances involvement of the bladder neck margin in a radical prostatectomy does not indicate that the tumor is pT4.
Regional Lymph Nodes (N)

NX   Regional lymph nodes cannot be assessed
N0   No regional lymph node metastasis
N1   Metastasis in regional lymph node or nodes

Distant Metastasis(*) (M)

MX   Distant metastasis cannot be assessed
M0   No distant metastasis
M1   Distant metastasis

     M1a Nonregional lymph node(s)
     M1b Bone(s)
     M1c Other site(s)


(*) When more than 1 site of metastasis is present, the most advanced category (pM1c) is used.
Stage Groupings (TNM)            Grade

Stage I     T1a     N0      M0   G1
Stage II    T1a     N0      M0   G2, G3-4
            T1b     N0      M0   Any G
            T1c     N0      M0   Any G
            T1      N0      M0   Any G
            T2      N0      M0   Any G
Stage III   T3      N0      M0   Any G
Stage IV    T4      N0      M0   Any G
            Any T   N1      M0   Any G
            Any T   Any N   M1   Any G


References

[1.] Young RH, Srigley JR, Amin MB, Ulbright TM, Cubilla A. Tumors of the Prostate Gland, Seminal Vesicle, Male Urethra and Penis. Washington, DC: Armed Forces Institute of Pathology Armed Forces Institute of Pathology A section of the US military which provides consultations, reference atlases and educational programs for pathologists . Atlas of Tumor Pathology; 3rd series. In press.

[2.] Gleason DR, Mellinger GT, the Veterans Administration Cooperative Urological Research Group. Prediction of prognosis for prostate adenocarcinoma by combined histological grading and clinical staging. J Urol. 1974;111:58-64.

[3.] Gleason DF. Histologic grading of prostate cancer: a perspective. Hum Pathol. 1992;23:273-279.

[4.] Bostwick DG. Gleason grading of prostatic needle biopsies: correlation with grade in 316 matched prostatectomies. Am J Surg Pathol. 1994;18:796-803.

[5.] Steinberg DM, Sauvageot J, Piantadosi S, Epstein JI. Correlation of prostate needle biopsy and radical prostatectomy Gleason grade in academic and community settings. Am J Surg Pathol. 1997;21:566-576.

[6.] Partin AW, Kattan MW, Subong ENP ENP European Neighbourhood Policy
ENP Everglades National Park
ENP Emergency Nurse Practitioner
ENP Emergency Number Professional (NENA)
ENP Enterprising Non-Profits
ENP Electroless Nickel Plating
ENP endotoxin-neutralizing protein
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[10.] Cupp MR, Bostwick DG, Myers RP, Oesterling JE. The volume of prostate cancer in the biopsy specimen cannot reliably predict the quantity of cancer in the radical prostatectomy on an individual basis. J Urol. 1995;153:1543-1548.

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[12.] Ravery V, Boccon-Gibod LA, Dauge-Geffroy, et al. Systematic biopsies accurately predict extracapsular extension of prostate cancer and persistent/recurrent detectable PSA (Professional Services Automation) An information system designed to organize, track and manage all opportunities, work, resources, costs, revenues and invoices to improve the productivity and efficiency of the workforce.  after radical prostatectomy. Urology. 1994;44:371-376.

[13.] Ravery V, Schmid HP, Toublanc M, Boccon-Gibod L. Is the percentage of cancer in biopsy cores predictive of extracapsular disease in T1-T2 prostate carcinoma? Cancer. 1996;78:1079-1084.

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A tumor marker associated with prostate cancer.

Mentioned in: Tumor Markers
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[15.] Stamey TA, Freiha FS, McNeal JE, et al. Localized prostate cancer: relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer. 1993;71;933-938.

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[17.] Ohori M, Scardino PT, Lapin SL, Seale-Hawkins C, Link J, Wheeler TM. The mechanisms and prognostic significance of seminal vesicle involvement by prostate cancer. Am J Surg Pathol. 1993;17:1252-1261.

[18.] Anderson PR, Hanlon Al, Patchefsky A, Al-Saleem T, Hanks GE. Perineural invasion and Gleason 7-10 tumors predict increased failure in prostate cancer patients with pretreatment pretreatment,
n the protocols required before beginning therapy, usually of a diagnostic nature; before treatment.

pretreatment estimate,
n See predetermination.
 PSA [is less than] 10 ng/ml treated with conformal con·for·mal  
adj.
1. Mathematics Designating or specifying a mapping of a surface or region upon another surface so that all angles between intersecting curves remain unchanged.

2.
 external beam radiation therapy. Int J Radiat Oncol Biol Phys. 1998;41:1087-1092.

[19.] Bastacky SI, Walsh PC, Epstein JI. Relationship between perineural tumor invasion on needle biopsy and radical prostatectomy capsular cap·su·lar  
adj.
Of, relating to, or resembling a capsule.

Adj. 1. capsular - resembling a capsule; "the capsular ligament is a sac surrounding the articular cavity of a freely movable joint and attached to the bones"
 penetration in clinical stage B adenocarcinoma of the prostate. Am J Surg Pathol. 1993;17:336-341.

[20.] Holmes GF, Walsh PC, Pound CR, Epstein JI. Excision of the neurovascular bundle at radical prostatectomy in cases with perineural invasion on needle biopsy. Urology. 1999;53:752-756.

[21.] Vargas SO, Jiroutek M, Welch MR, et al. Perineural invasion in prostate needle biopsy specimens: correlation with extraprostatic extension at resection. Am J Clin Pathol. 1999;111:223-228.

[22.] Egan AJM AJM American Journal of Medicine
AJM Air Jamaica (ICAO code)
AJM Abrasive Jet Machining
AJM Assistant Jumpmaster (US Army)
AJM Apprentice-Journeyman-Master
AJM A. J.
, Bostwick DG. Prediction of extraprostatic extension of prostate cancer on needle biopsy findings: perineural invasion lacks significance on multivariate analysis. Am J Surg Pathol. 1998;21:1496-1500.

[23.] National Prostate Cancer Detection Project. Workshop on Prostatic Intraepithelial Neoplasia: significance and correlation with prostatic specific antigen and transrectal ultrasound. Urology. 1989;34(6 suppl).

[24.] Bostwick DG. Prospective origins of prostate carcinoma: prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia. Cancer. 1996;78:330-336.

[25.] Bostwick DG. High-grade prostatic intraepithelial neoplasia: the most likely precursor of prostatic cancer. Cancer. 1995;75:1823-1836.

[26.] Graham SD Jr, Bostwick DG, Hoisaeter A, et al. Report of the Committee on Staging and Pathology: International Workshop on Prostatic Cancer and Hyperplasia. Cancer. 1992;70 (1 suppl):359-361.

[27.] Humphrey PA, Walther PJ. Adenocarcinoma of the prostate, h simple sampling considerations. Am J Clin Pathol. 1993;99:746-759.

[28.] Grignon DJ, Sakr WA. Pathologic staging of prostate carcinoma: what are the issues? Cancer. 1996;78:337-340.

[29.] Epstein JI. The evaluation of radical prostatectomy specimens: therapeutic and prognostic implications. Pathol Annu. 1991;26:159-210.

[30.] Bostwick DG, Montironi R. Evaluating radical prostatectomy specimens: therapeutic and prognostic importance. Virchows Arch. 1997;430:1-16.

[31.] Sakr WA, Wheeler TM, Blute M, et al. Staging and reporting of prostate cancer: sampling of the radical prostatectomy specimen. Cancer. 1996;78:366-369.

[32.] Blute ML, Bostwick DG, Seay TM, et al. Pathologic classification of prostate carcinoma: impact of margin status. Cancer. 1998;82:902-908.

[33.] Epstein JI, Sauvageot J. Do close but negative margins in radical prostatectomy specimens increase the risk of postoperative progression? J Urol. 1997; 157:241-243.

[34.] Graefen M, Hammerer P, Michl U, et al. Incidence of positive surgical margins after biopsy-selected nerve-sparing radical prostatectomy. Urology. 1998; 51:437-442.

[35.] Ohori M, Wheeler T, Kattan MW, et al. Prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol. 1995;154:1818-1824.

[36.] Weldon VE, Tavel FR, Neuwirth H, Cohen cohen
 or kohen

(Hebrew: “priest”) Jewish priest descended from Zadok (a descendant of Aaron), priest at the First Temple of Jerusalem. The biblical priesthood was hereditary and male.
 R. Patterns of positive specimen margins and detectable prostate specific antigen after radical perineal prostatectomy Radical perineal prostatectomy is a surgical procedure wherein the prostate gland is removed through an incision in the area between the anus and the scrotum (perineum). It is typically performed to remove early prostate cancer. . J Urol. 1995;153:1565-1569.

[37.] Fleming ID, Cooper JS, Henson DE, et al, eds. AJCC Manual for Staging of Cancer. 5th ed. Philadelphia, Pa: Lippincott Raven; 1997.

[38.] Sobin LH, Wittekind C, eds. TNM Classification of Malignant Tumours. 5th ed. International Union Against Cancer. New York, NY: Wiley; 1997.

Accepted for publication February 1, 2000.

From McMaster University, Hamilton, Ontario, Canada (Dr Srigley); Emory University, Atlanta, Ga (Dr Amin); Bostwick Laboratories, Richmond, Va (Dr Bostwick); Wayne State University Wayne State University, at Detroit, Mich.; state supported; coeducational; established 1956 as a successor to Wayne Univ. (formed 1934 by a merger of five city colleges). , Detroit, Mich (Dr Grignon); and the University of Utah The University of Utah (also The U or the U of U or the UU), located in Salt Lake City, is the flagship public research university in the state of Utah, and one of 10 institutions that make up the Utah System of Higher Education.  School of Medicine, Salt Lake City, Utah For ships of the United States Navy of the same name, see .
Salt Lake City is the capital and the most populous city of the U.S. state of Utah. The name of the city is often shortened to Salt Lake, or its initials, S.L.C.
 (Dr Hammond).

Originally published in the Archives of Pathology & Laboratory Medicine, August 1994.

Reprints: Joe Schramm, College of American Pathologists This article or section needs sources or references that appear in reliable, third-party publications. Alone, primary sources and sources affiliated with the subject of this article are not sufficient for an accurate encyclopedia article. , 325 Waukegan Rd, Northfield, Ill.
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Author:Srigley, John R.; Amin, Mahul B.; Bostwick, David G.; Grignon, David J.; Hammond, M. Elizabeth H.
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Statistical Data Included
Geographic Code:1USA
Date:Jul 1, 2000
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