Krukenberg tumor
Encyclopedia
A Krukenberg tumor refers to a malignancy in the ovary that metastasized
from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus
, is the most common source. Krukenberg tumors are often (over 80%) found in both ovaries, consistent with its metastatic nature.
(1871–1946), who reported what he thought was a new type of primary ovarian malignancy in 1896; six years later these were shown to be of metastatic gastrointestinal tract origin. However, Paget had described the process in 1854.
to the ovary accounts for only about 1 to 2% of ovarian cancer
; in the remainder, the ovary itself is the primary cancer site. However, in Japan they represent a much higher percentage of malignancies in the ovary (almost 20%) due to the increased prevalence of gastric cancer.
Krukenberg tumors account for about 15% of metastatic cancers that initially appear to have arisen in the ovary, and as such is less common than metastasis arising from ovarian epithelial and germ-cell tumors.
In people who have had nongynecologic malignancy, approximately 20% of adnexa
l masses are malignant, and 60% of these are Krukenberg tumors.
, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism
, or occasionally virilization
as a main symptom.
All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography
(CT) scans, laparotomy
and/or a biopsy
of the ovary.
Microscopically, Krukenberg tumors are often characterized by mucin
-secreting signet-ring cells in the tissue of the ovary; when the primary tumor is discovered, the same signet-ring cells are typically found. However, other microscopic features can predominate. Krukenberg tumors are most commonly metastases from gastric cancer, particularly adenocarcinoma
, or breast cancer
particularly invasive lobular breast carcinoma
, but they can arise in the appendix, colon, small intestine, rectum, gallbladder, and urinary bladder or gallbladder, biliary tract, pancreas, ampulla of Vater or uterine cervix.
Immunohistochemistry
may help in diagnosing Krukenberg tumors from primary ovarian neoplasms but needs to be applied with discretion. For example, tumors that are immunoreactive to CEA
or cytokeratin 20
(CK20) and negative for cytokeratin 7
(CK7) may be more likely to be of colorectal origin.
and/or radiotherapy is uncertain but may be sometimes be beneficial.
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus
Pylorus
The pylorus is the region of the stomach that connects to the duodenum . It is divided into two parts:* the pyloric antrum, which connects to the body of the stomach.* the pyloric canal, which connects to the duodenum....
, is the most common source. Krukenberg tumors are often (over 80%) found in both ovaries, consistent with its metastatic nature.
Historical
Krukenberg tumors are named after Friedrich Ernst KrukenbergFriedrich Ernst Krukenberg
Friedrich Ernst Krukenberg was a German physician who was a native of Halle an der Saale. He was a brother to orthopedic surgeon Hermann Krukenberg , and Georg Heinrich Peter Krukenberg , who was a professor of gynecology at the University of Bonn.Krukenberg originally studied in his native city...
(1871–1946), who reported what he thought was a new type of primary ovarian malignancy in 1896; six years later these were shown to be of metastatic gastrointestinal tract origin. However, Paget had described the process in 1854.
Etiology and incidence
Krukenberg tumors can be seen in all age groups, with an average age of 45 years. In most countries, cancer that has metastasizedMetastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
to the ovary accounts for only about 1 to 2% of ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
; in the remainder, the ovary itself is the primary cancer site. However, in Japan they represent a much higher percentage of malignancies in the ovary (almost 20%) due to the increased prevalence of gastric cancer.
Krukenberg tumors account for about 15% of metastatic cancers that initially appear to have arisen in the ovary, and as such is less common than metastasis arising from ovarian epithelial and germ-cell tumors.
In people who have had nongynecologic malignancy, approximately 20% of adnexa
Adnexa of uterus
The adnexa of uterus refers to the structures most closely related structurally and functionally to the uterus.-Terminology:It can be defined in slightly different ways:...
l masses are malignant, and 60% of these are Krukenberg tumors.
Symptoms
Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascitesAscites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism
Hirsutism
Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
, or occasionally virilization
Virilization
In biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...
as a main symptom.
All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT) scans, laparotomy
Laparotomy
A laparotomy is a surgical procedure involving a large incision through the abdominal wall to gain access into the abdominal cavity. It is also known as coeliotomy.- Terminology :...
and/or a biopsy
Biopsy
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...
of the ovary.
Pathogenesis
There has been debate over the exact mechanism of metastasis of the tumor cells from the stomach, appendix or colon to the ovaries. Classically it was thought that direct seeding across the abdominal cavity accounted for the spread of this tumor, but spread by way of the lymphatic is considered more likely. The average age of diagnosis of Krukenberg tumors may partly relate to the relatively increased vascularity of the ovaries.Microscopically, Krukenberg tumors are often characterized by mucin
Mucin
Mucins are a family of high molecular weight, heavily glycosylated proteins produced by epithelial tissues in most metazoans. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell...
-secreting signet-ring cells in the tissue of the ovary; when the primary tumor is discovered, the same signet-ring cells are typically found. However, other microscopic features can predominate. Krukenberg tumors are most commonly metastases from gastric cancer, particularly 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...
, or breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
particularly invasive lobular breast carcinoma
Invasive lobular carcinoma
Invasive lobular carcinoma accounts for 5-10% of invasive breast cancer.The histologic patterns include: Overall, the 5-year survival rate of invasive lobular carcinoma was approximately 85% in 2003....
, but they can arise in the appendix, colon, small intestine, rectum, gallbladder, and urinary bladder or gallbladder, biliary tract, pancreas, ampulla of Vater or uterine cervix.
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...
may help in diagnosing Krukenberg tumors from primary ovarian neoplasms but needs to be applied with discretion. For example, tumors that are immunoreactive to CEA
Cea
-People:* Eusebio Rodolfo Cordón Cea , Salvadoran politician* José Pedro Cea , Uruguayan footballer* José Roberto Cea , Salvadoran novelist and poet-Places:* Cea River, Spain...
or cytokeratin 20
Keratin 20
Keratin 20, often abbreviated CK20, is a protein that in humans is encoded by the KRT20 gene.Keratin 20 is a type I cytokeratin. It is a major cellular protein of mature enterocytes and goblet cells and is specifically found in the gastric and intestinal mucosa....
(CK20) and negative for cytokeratin 7
Keratin 7
Keratin, type I cytoskeletal 7 also known as cytokeratin-7 or keratin-7 or sarcolectin is a protein that in humans is encoded by the KRT7 gene. Keratin 7 is a type II keratin...
(CK7) may be more likely to be of colorectal origin.
Treatment and prognosis
Since Krukenberg tumors are secondary (metastatic), management might logically be driven by identifying and treating the primary cancer. The optimal treatment of Krukenberg tumors is unclear. The role of surgical resection has not been adequately addressed but if metastasis is limited to the ovaries, surgery may improve survival. The role of chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and/or radiotherapy is uncertain but may be sometimes be beneficial.