Krukenberg tumor

Signet ring cell carcinoma metastasis to the ovary, also called Krukenberg tumor: Gross pathology (top, cross-section at right) and histopathology at low and high magnification. The latter shows invasive proliferation of signet-ring cells with a desmoplastic stroma.
Specialty| Oncology

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.[1] Gastric adenocarcinoma, especially at the pylorus, is the most common source.[2] Krukenberg tumors are often (over 80%)[2] found in both ovaries, consistent with its metastatic nature.[2]

## Contents

* 1 Signs and symptoms
* 2 Cause
* 3 Pathogenesis
* 4 Diagnosis
* 5 Treatment
* 6 Incidence
* 7 History
* 8 References
* 9 External links

## Signs and symptoms[edit | edit source]

Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, 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,[3] or occasionally virilization[4] as a main symptom. In rare cases the disease can manifest with hydronephrosis and hydroureter.[5]

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.

## Cause[edit | edit source]

Krukenberg tumors can be seen in all age groups, with an average age of 45 years.[2] In most countries, cancer that has metastasized to the ovary accounts for only about 1 to 2% of ovarian cancer;[2] 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.[2]

## Pathogenesis[edit | edit source]

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.[2] Retrograde lymphatics are thought to be more important in the pathogenesis of Krukenberg tumour, since the ovaries in Krukenberg tumour do not show capsular invasion or a breech of the epithelium lining the surface. The average age of diagnosis of Krukenberg tumors may partly relate to the relatively increased vascularity of the ovaries.[6]

Microscopically, Krukenberg tumors are often characterized by mucin-secreting signet-ring cells in the tissue of the ovary;[6] when the primary tumor is discovered, the same signet-ring cells are typically found. However, other microscopic features can predominate.[6][3] Krukenberg tumors are most commonly metastases from gastric cancer, particularly adenocarcinoma, or breast cancer[1] particularly invasive lobular breast carcinoma,[2] but they can arise in the appendix, colon, small intestine, rectum, gallbladder, and urinary bladder[3] or gallbladder, biliary tract, pancreas, ampulla of Vater or uterine cervix.[2]

Immunohistochemistry may help in diagnosing Krukenberg tumors from primary ovarian neoplasms[6] but needs to be applied with discretion.[7] 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.[2]

## Diagnosis[edit | edit source]

Computed tomography of Krukenberg tumor

In terms of the diagnosis of krukenburg tumors the following is done:[8]

* CT scan
* Ultrasound
* CA-125 Test (elevated)

## Treatment[edit | edit source]

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.[2] The role of surgical resection has not been adequately addressed[2] but if metastasis is limited to the ovaries, surgery may improve survival.[2][9][10] The role of chemotherapy and/or radiotherapy is uncertain[2] but may sometimes be beneficial.[10]

## Incidence[edit | edit source]

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.[citation needed]

In people who have had nongynecologic malignancy, approximately 20% of adnexal masses are malignant, and 60% of these are Krukenberg tumors.[11]

## History[edit | edit source]

Krukenberg tumors are named after Friedrich Ernst Krukenberg (1871–1946),[12] 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.[6] However, Paget had described the process in 1854.[6]

## References[edit | edit source]

1. ↑ 1.0 1.1 Ackerman LV, Rosai J (2004). Rosai and Ackerman's surgical pathology. Vol. 2\. St. Louis: Mosby. p. 1708\. ISBN 0-323-01342-2.
2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 Al-Agha OM, Nicastri AD (November 2006). "An in-depth look at Krukenberg tumor: an overview". Archives of Pathology & Laboratory Medicine. 130 (11): 1725–1730. doi:10.5858/2006-130-1725-AILAKT. PMID 17076540.
3. ↑ 3.0 3.1 3.2 Kiyokawa T, Young RH, Scully RE (March 2006). "Krukenberg tumors of the ovary: a clinicopathologic analysis of 120 cases with emphasis on their variable pathologic manifestations". The American Journal of Surgical Pathology. 30 (3): 277–299. doi:10.1097/01.pas.0000190787.85024.cb. PMID 16538048. S2CID 10359707.
4. ↑ Papakonstantinou E, Liapis A, Kairi-Vassilatou E, Iavazzo C, Kleanthis CK, Kondi-Pafiti A (2011). "Virilizing ovarian Krukenberg tumor in a 27-year-old pregnant woman. A case report and literature review". European Journal of Gynaecological Oncology. 32 (3): 331–333. PMID 21797128.
5. ↑ Todorov A, Sirakov N, Angelova I, Chervenkov L, Sirakov V, Georiev A, Stoeva M (2016). "The Leading Role of Computer Tomography for the Diagnose of Krukenberg Tumor With a Typical Symptomatology". Medical Physics International Journal. 4 (1): 59–60. ISSN 2306-4609.
6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Young RH (September 2006). "From krukenberg to today: the ever present problems posed by metastatic tumors in the ovary: part I. Historical perspective, general principles, mucinous tumors including the krukenberg tumor". Advances in Anatomic Pathology. 13 (5): 205–227. doi:10.1097/01.pap.0000213038.85704.e4. PMID 16998315. S2CID 9598841.
7. ↑ Young RH (May 2007). "From Krukenberg to today: the ever present problems posed by metastatic tumors in the ovary. Part II". Advances in Anatomic Pathology. 14 (3): 149–177. doi:10.1097/PAP.0b013e3180504abf. PMID 17452813. S2CID 5609922.
8. ↑ Aziz, Muhammad; Killeen, Robert B.; Kasi, Anup (2022). "Krukenberg Tumor". StatPearls. StatPearls Publishing. Archived from the original on 19 July 2022. Retrieved 1 December 2022.
9. ↑ Cheong JH, Hyung WJ, Chen J, Kim J, Choi SH, Noh SH (August 2004). "Survival benefit of metastasectomy for Krukenberg tumors from gastric cancer". Gynecologic Oncology. 94 (2): 477–482. doi:10.1016/j.ygyno.2004.05.007. PMID 15297191.
10. ↑ 10.0 10.1 Kim WY, Kim TJ, Kim SE, Lee JW, Lee JH, Kim BG, Bae DS (March 2010). "The role of cytoreductive surgery for non-genital tract metastatic tumors to the ovaries". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 149 (1): 97–101. doi:10.1016/j.ejogrb.2009.11.011. PMID 20018420.
11. ↑ Juretzka MM, Crawford CL, Lee C, Wilton A, Schuman S, Chi DS, et al. (May 2006). "Laparoscopic findings during adnexal surgery in women with a history of nongynecologic malignancy". Gynecologic Oncology. 101 (2): 327–330. doi:10.1016/j.ygyno.2005.10.025. PMID 16360202.
12. ↑ Friedrich Ernst Krukenberg at Who Named It?

## External links[edit | edit source]

Classification|

* ICD-10: C56
* ICD-9-CM: 183
* ICD-O: 8490/6
* MeSH: D007725
* DiseasesDB: 30081

|

* 00498 at CHORUS

* v
* t
* e

Glandular and epithelial cancer

Epithelium|

| Papilloma/carcinoma|

* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
* Squamous cell carcinoma
* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma

|

Complex epithelial|

* Warthin's tumor
* Thymoma
* Bartholin gland carcinoma

Glands|

| Adenomas/
adenocarcinomas|

| Gastrointestinal|

* tract: Linitis plastica
* Familial adenomatous polyposis

* pancreas
* Insulinoma
* Glucagonoma
* Gastrinoma
* VIPoma
* Somatostatinoma

* Cholangiocarcinoma
* Klatskin tumor
* Hepatocellular adenoma/Hepatocellular carcinoma

|

Urogenital|

* Renal cell carcinoma
* Endometrioid tumor
* Renal oncocytoma

Endocrine|

* Prolactinoma
* Multiple endocrine neoplasia
* Adrenocortical adenoma/Adrenocortical carcinoma
* Hürthle cell

Other/multiple|

* Neuroendocrine tumor
* Carcinoid
* Adenoid cystic carcinoma
* Oncocytoma
* Clear-cell adenocarcinoma
* Apudoma
* Cylindroma
* Papillary hidradenoma

Adnexal and
skin appendage|

* sweat gland
* Hidrocystoma
* Syringoma
* Syringocystadenoma papilliferum

Cystic, mucinous,
and serous|

| Cystic general|

* Cystadenoma/Cystadenocarcinoma

|

Mucinous|

* Signet ring cell carcinoma
* Krukenberg tumor
* Mucinous cystadenoma / Mucinous cystadenocarcinoma
* Pseudomyxoma peritonei
* Mucoepidermoid carcinoma

Serous|

* Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma

Ductal, lobular,
and medullary|

| Ductal carcinoma|

* Mammary ductal carcinoma
* Pancreatic ductal carcinoma
* Comedocarcinoma
* Paget's disease of the breast / Extramammary Paget's disease

|

Lobular carcinoma|

* Lobular carcinoma in situ
* Invasive lobular carcinoma

Medullary carcinoma|

* Medullary carcinoma of the breast
* Medullary thyroid cancer

Acinar cell|

* Acinic cell carcinoma

* v
* t
* e

Tumors of the female urogenital system

Adnexa|

| Ovaries|

| Glandular and epithelial/
surface epithelial-
stromal tumor|

| CMS:|

* Ovarian serous cystadenoma
* Mucinous cystadenoma
* Cystadenocarcinoma
* Papillary serous cystadenocarcinoma
* Krukenberg tumor

|

* Endometrioid tumor
* Clear-cell ovarian carcinoma
* Brenner tumour

Sex cord–gonadal stromal|

* Leydig cell tumour
* Sertoli cell tumour
* Sertoli–Leydig cell tumour
* Thecoma
* Granulosa cell tumour
* Luteoma
* Sex cord tumour with annular tubules

Germ cell|

* Dysgerminoma
* Nongerminomatous
* Embryonal carcinoma
* Endodermal sinus tumor
* Gonadoblastoma
* Teratoma/Struma ovarii
* Choriocarcinoma

Fibroma|

* Meigs' syndrome

Fallopian tube|

* Adenomatoid tumor

Uterus|

| Myometrium|

* Uterine fibroids/leiomyoma
* Leiomyosarcoma
* Adenomyoma

|

Endometrium|

* Endometrioid tumor
* Uterine papillary serous carcinoma
* Endometrial intraepithelial neoplasia
* Uterine clear-cell carcinoma

Cervix|

* Cervical intraepithelial neoplasia
* Clear-cell carcinoma
* SCC
* Glassy cell carcinoma
* Villoglandular adenocarcinoma

Placenta|

* Choriocarcinoma
* Gestational trophoblastic disease

General|

* Uterine sarcoma
* Mixed Müllerian tumor

Vagina|

* Squamous-cell carcinoma of the vagina
* Botryoid rhabdomyosarcoma
* Clear-cell adenocarcinoma of the vagina
* Vaginal intraepithelial neoplasia
* Vaginal cysts

Vulva|

* SCC
* Melanoma
* Papillary hidradenoma
* Extramammary Paget's disease
* Vulvar intraepithelial neoplasia
* Bartholin gland carcinoma

* v
* t
* e

Digestive system neoplasia

GI tract|

| Upper|

| Esophagus|

* Squamous cell carcinoma
* Adenocarcinoma

|

Stomach|

* Gastric carcinoma
* Signet ring cell carcinoma
* Gastric lymphoma
* MALT lymphoma
* Linitis plastica
* Hereditary diffuse gastric cancer

Lower|

| Small intestine|

* Duodenal cancer
* Adenocarcinoma

|

Appendix|

* Carcinoid
* Pseudomyxoma peritonei

Colon/rectum|

* Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers

Cronkhite–Canada

* Polyposis syndromes: Juvenile
* MUTYH-associated
* Familial adenomatous/Gardner's
* Polymerase proofreading-associated
* Serrated polyposis

* Neoplasm: Adenocarcinoma
* Familial adenomatous polyposis
* Hereditary nonpolyposis colorectal cancer

Anus|

* Squamous cell carcinoma

Upper and/or lower|

* Gastrointestinal stromal tumor
* Krukenberg tumor (metastatic)

Accessory|

| Liver|

* malignant: Hepatocellular carcinoma
* Fibrolamellar
* Hepatoblastoma

* benign: Hepatocellular adenoma
* Cavernous hemangioma

* hyperplasia: Focal nodular hyperplasia
* Nodular regenerative hyperplasia

|

Biliary tract|

* bile duct: Cholangiocarcinoma
* Klatskin tumor

* gallbladder: Gallbladder cancer

Pancreas|

* exocrine pancreas: Adenocarcinoma
* Pancreatic ductal carcinoma

* cystic neoplasms: Serous microcystic adenoma
* Intraductal papillary mucinous neoplasm
* Mucinous cystic neoplasm
* Solid pseudopapillary neoplasm

* Pancreatoblastoma

Peritoneum|

* Primary peritoneal carcinoma
* Peritoneal mesothelioma
* Desmoplastic small round cell tumor

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