High-grade prostatic intraepithelial neoplasia
Encyclopedia
In urologic pathology
, high-grade prostatic intraepithelial neoplasia, abbreviated HGPIN, is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer
).
It may be referred to simply as prostatic intraepithelial neoplasia (abbreviated as PIN). It is considered to be a pre-malignancy, or carcinoma in situ
, of the prostatic gland
s.
and very frequently seen in prostates removed for prostate cancer.
, given a history of a HGPIN diagnosis
, the chance of finding prostatic adenocarcinoma
is approximately 30%.
Blood test
s for prostate specific antigen
(PSA), digital rectal examination, ultrasound scanning of the prostate via the rectum
, fine needle aspiration or medical imaging
studies (such as magnetic resonance imaging
) are not useful for diagnosing HGPIN.
Its cytologic
features are that of prostatic adenocarcinoma:
Microscopically
, PIN is a collection of irregular, atypical epithelial
cell
s. The architecture of the glands and ducts remains normal. The epithelial cells proliferate and crowding results in a pseudo-multilayer
appearance. They remain fully contained within a prostate acinus
(the berry-shaped termination of a gland, where the secretion is produced) or duct. The latter can be demonstrated with special staining techniques (immunohistochemistry
for cytokeratin
s) to identify the basal cells forming the supporting layer of the acinus. In prostate cancer, the abnormal cells spread beyond the boundaries of the acinus and form clusters without basal cells. In HGPIN, the basal cell layer is disrupted but present.
Because it is thought to be a premalignant state, PIN is often considered the prostate equivalent of what is called carcinoma in situ
(localized cancer) in other organs. However, PIN differs from carcinoma in situ in that it may remain unchanged or even spontaneously regress.
Several architectural variants of PIN have been described, and many cases have multiple patterns. The main ones are tufting, micropapillary, cribriform, and flat. Although these different appearances may cause confusion with other conditions, they have not been found to be of clinical importance. Rarer types are signet-ring-cell, small-cell-neuroendocrine, mucinous, foamy, inverted, and with squamous differentiation.
The risk for men with high grade PIN of being diagnosed with prostate cancer after repeat biopsy has decreased since the introduction of biopsies at more than six locations (traditional sextant biopsies).
The exact timing of repeat biopsies remains an area of controversy, as the time required for, and probability of HGPIN transformations to prostate cancer are not well understood.
reports. As such, PIN has become synonymous with high grade PIN.
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
, high-grade prostatic intraepithelial neoplasia, abbreviated HGPIN, is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
).
It may be referred to simply as prostatic intraepithelial neoplasia (abbreviated as PIN). It is considered to be a pre-malignancy, or carcinoma in situ
Carcinoma in situ
Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...
, of the prostatic gland
Gland
A gland is an organ in an animal's body that synthesizes a substance for release of substances such as hormones or breast milk, often into the bloodstream or into cavities inside the body or its outer surface .- Types :...
s.
Signs and symptoms
HGPIN in isolation is asymptomatic. It is typically discovered in prostate biopsies taken to rule-out prostate cancerProstate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
and very frequently seen in prostates removed for prostate cancer.
Prognosis
On a subsequent biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
, given a history of a HGPIN diagnosis
Diagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
, the chance of finding prostatic adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
is approximately 30%.
Diagnosis
HGPIN is diagnosed from tissue by a pathologist, which may be come from:- a needle biopsyBiopsyA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
taken via the rectumRectumThe rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
and, - surgicalSurgerySurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
removal of prostate tissue:- transurethral resection of the prostateTransurethral resection of the prostateTransurethral resection of the prostate is a urological operation. It is used to treat benign prostatic hyperplasia . As the name indicates, it is performed by visualising the prostate through the urethra and removing tissue by electrocautery or sharp dissection...
- removal of extra prostate tissue to improve urination (a treatment for benign prostatic hyperplasiaBenign prostatic hyperplasiaBenign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....
), - Radical prostatectomy) - complete removal of prostate and seminal vesicles (a treatment for prostate cancer).
- transurethral resection of the prostate
Blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s for prostate specific antigen
Prostate specific antigen
Prostate-specific antigen also known as gamma-seminoprotein or kallikrein-3 is a glycoprotein that in humans is encoded by the KLK3 gene. KLK3 is a member of the kallikrein-related peptidase family that are secreted by the epithelial cells of the prostate gland...
(PSA), digital rectal examination, ultrasound scanning of the prostate via the rectum
Transrectal ultrasonography
Transrectal ultrasound create an image of organs in the pelvis. The most common indication for transrectal ultrasound is for the evaluation of the prostate gland in men with elevated prostate specific antigen or prostatic nodules on digital rectal exam. Ultrasound may reveal prostate cancer, benign...
, fine needle aspiration or medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
studies (such as magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
) are not useful for diagnosing HGPIN.
Histology
HGPIN typically has one of four different histologic patterns:- tuftTuftIn the aviation field, the term tuft refers to a strip of yarn or string of varying length attached to an aircraft surface in a grid pattern and imaged during flight. The motion of these tufts during flight can be observed and recorded in order to locate flow features such as boundary layer...
ed, - micropapillary,
- cribriform and,
- flat.
Its cytologic
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
features are that of prostatic adenocarcinoma:
- presence of nucleoli,
- increased nuclear-to-cytoplasmic ratioNC ratioThe nuclear-cytoplasmic ratio is a measurement used in cell biology...
and, - increased nuclear size.
Microscopically
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
, PIN is a collection of irregular, atypical epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s. The architecture of the glands and ducts remains normal. The epithelial cells proliferate and crowding results in a pseudo-multilayer
Pseudostratified epithelium
A pseudostratified epithelium is a type of epithelium that, though comprising only a single layer of cells, has its cell nuclei positioned in a manner suggestive of stratified epithelia...
appearance. They remain fully contained within a prostate acinus
Acinus
An acinus refers to any cluster of cells that resembles a many-lobed "berry," such as a raspberry...
(the berry-shaped termination of a gland, where the secretion is produced) or duct. The latter can be demonstrated with special staining techniques (immunohistochemistry
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
for cytokeratin
Cytokeratin
Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue. The term "cytokeratin" began to be used in the late 1970s when the protein subunits of keratin intermediate filaments inside cells were first being identified and...
s) to identify the basal cells forming the supporting layer of the acinus. In prostate cancer, the abnormal cells spread beyond the boundaries of the acinus and form clusters without basal cells. In HGPIN, the basal cell layer is disrupted but present.
Because it is thought to be a premalignant state, PIN is often considered the prostate equivalent of what is called carcinoma in situ
Carcinoma in situ
Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...
(localized cancer) in other organs. However, PIN differs from carcinoma in situ in that it may remain unchanged or even spontaneously regress.
Several architectural variants of PIN have been described, and many cases have multiple patterns. The main ones are tufting, micropapillary, cribriform, and flat. Although these different appearances may cause confusion with other conditions, they have not been found to be of clinical importance. Rarer types are signet-ring-cell, small-cell-neuroendocrine, mucinous, foamy, inverted, and with squamous differentiation.
Relation to prostate cancer
There are several reasons why PIN is the most likely prostate cancer precursor. PIN is more common in men with prostate cancer. High grade PIN can be found in 85 to 100% of radical prostatectomy specimens, nearby or even in connection with prostate cancer. It tends to occur in the peripheral zone of the prostate. With age, it becomes increasingly multifocal, like prostate cancer. Molecular analysis has shown that high grade PIN and prostate cancer share many genetic abnormalities. This has been confirmed in a transgenic mouse model.The risk for men with high grade PIN of being diagnosed with prostate cancer after repeat biopsy has decreased since the introduction of biopsies at more than six locations (traditional sextant biopsies).
Treatment
HGPIN in isolation does not require treatment. In prostate biopsies it is not predictive of prostate cancer in one year if the prostate was well-sampled, i.e. if there were more than 8 cores.The exact timing of repeat biopsies remains an area of controversy, as the time required for, and probability of HGPIN transformations to prostate cancer are not well understood.
History
PIN was historically subdivided into different stages, based on the level of cell atypia. PIN was formerly classified as PIN 1, 2 or 3, in order of increasing cell irregularities. Nowadays, PIN 1 is referred to as low grade PIN, and PIN 2 and PIN 3 are grouped together as high grade PIN. Only high grade PIN has been shown to be a risk factor for prostate cancer. Because low grade PIN has no significance and does not require repeat biopsies or treatment, it is not mentioned in pathologyPathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
reports. As such, PIN has become synonymous with high grade PIN.
External links
- Prostatic intraepithelial neoplasia - prostate-cancer.org.