Krukenberg Tumor

Continuing Education Activity

Krukenburg tumor is a metastatic malignancy of the ovary characterized by mucin-rich signet-ring adenocarcinoma that primarily arises from a gastrointestinal site in most cases and less commonly from other sites. Often these tumors are bilateral (over 80%), given its metastatic nature. This activity reviews the pathophysiology of krukenberg tumor and highlights the role of the interprofessional team in its management.


  • Describe the pathophysiology of krukenberg tumor.
  • Review the presentation of krukenberg tumor.
  • Summarize the treatment options for krukenberg tumor.
  • Explain the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by krukenberg tumor.


Krukenburg tumor is a metastatic malignancy of the ovary characterized by mucin-rich signet-ring adenocarcinoma that primarily arises from a gastrointestinal site in most cases and less commonly from other sites. Often these tumors are bilateral (over 80%), given its metastatic nature. This tumor is named after Friedrich Ernst Krukenberg (1871-1946), who reported a new type of ovarian malignancy in 1896. This was discovered to be metastatic in origin from primary gastrointestinal site 6 years later[1][2][3].


In most cases, the stomach has been attributed to be the primary site with studies showing this to be in about 70% of cases. Gastric and colorectal cancers collectively account for almost 90% of the primary site for this tumor. Other less common primary sites described in the literature are breast, appendix, small intestine, gallbladder, urinary bladder, biliary tract, pancreas, ampulla of Vater, or uterine cervix[1][2][4].


The average age of diagnosis is 45 years. However, it can be seen in all age groups. Of all the ovarian tumors diagnosed, Krukenburg tumors make up about 1% to 2% of these tumors. The incidence is higher in countries like Korea, Japan, and China where the tumor makes up about 20% of all ovarian cancers[1].


The exact mechanism of tumor spread is still unknown. The tumor is thought to spread via 1 of the 3 mechanisms: (1) the lymphatic system, (2) the hematogenous system, or (3) the transcoelomic pathway. Hematogenous and lymphatic pathway means the tumor spreads through blood vessels or lymphatic channel respectively. Transcoelomic pathway means the actual cancer cells directly spread through abdominal route to adjacent organs. Given the tumor is diagnosed at an advanced age, it is believed that the tumor metastasizes through mixed pathways. The average age of diagnosis co-relates to increased vascularity of the ovaries which supports the lymphatic and hematogenous spread hypothesis[5][6][7].

The lymphatic route is believed to be the most likely route of cancer spread with several supporting evidence[6]:

  1. Microscopically, the hilum and cortex have demonstrated lymphatic permeation
  2. Many cases have been reported where primary tumor is confined to mucosa and submucosa, and given the rich lymphatic network in the gastrointestinal mucosa and submucosa, the only logical explanation is that the tumor spread through this pathway
  3. The risk of metastasis is higher with increased number of positive metastatic lymph nodes
  4. Lack of involvement of the peritoneum without any evidence of seedings, adhesion, or tumor infiltrates favors other pathways as opposed to the transcoelomic route.


Grossly, the ovaries are asymmetrically enlarged with a bosselated contour. They are usually solid, but can occasionally be cystic. The capsular surface is mostly free of any tumor infiltrates, adhesions, implants or deposits which can be deceptive and appear as a primary ovarian tumor.

The characteristic finding of this tumor is the presence of mucin-laden signet-ring cells, which is present in at least 10% of the cases. The diagnostic criteria of WHO based on Serov and Scully description are for making the diagnosis states:

  1. The presence of stromal involvement
  2. Ovarian stromal sarcomatoid proliferation
  3. The presence of mucin-producing signet-ring cells

Histochemically, the intracytoplasmic mucins of the signet-ring is neutral and acidic and stains with Mayer mucicarmine, periodic acid-Schiff with diastase digestion, and Alcian blue stain. Immunohistochemically, these tumors stain positive for cytokeratin (AE1/AE3), and epithelial membrane antigen and they stain negative for inhibin and vimentin[1][2].

History and Physical

These tumors can be asymptomatic or may manifest with non-specific gastrointestinal signs and symptoms as abdominal or pelvic pain, bloating, ascites, or dyspareunia. These tumors can become autonomous and produce hormones leading to vaginal bleeding, menstrual cycle irregularities, hirsutism, or rarely virilization[1].


Given the non-specific signs and symptoms, work-up involves obtaining imaging including computed tomography (CT) scan or ultrasound of the abdomen and pelvis. These tumors often appear as bilateral ovarian masses and usually appear solid but can also be cystic. Pre-operative level for serum CA-125 can be elevated and decreases after tumor resection. These levels can be used for:

  1. Follow-up of patients after surgery to document complete resection as levels will decline
  2. Follow-up of patients to diagnose metastatic spread to ovaries in patients with history of other cancers (e.g., gastrointestinal, breast)
  3. To predict the prognosis of patients with Krukenburg tumors; one study showed that levels greater than 75 U/ml were associated with decreased 5-year survival than patients with lower levels[1][2].

Treatment / Management

No optimal treatment strategy for these tumors has been established. Radiation therapy has no significant role in the prognosis of patients with Krukenberg tumor. Similarly, chemotherapy has not demonstrated any benefits for these patients. Given the metastatic nature and lower rate of resectability, surgery is deferred as it does not offer any increased survival time. However, if the metastasis is primarily limited to ovaries, then surgery may offer increased survival time[1][2]. A retrospective analysis showed that patients who underwent palliative surgeries including unilateral or bilateral salpingo-opherectomy alone, or a total hyseterectomy combined with bilateral salpingo-opherectomy, had a median overall survival of 17 months[8].

Differential Diagnosis

Classic Krukenberg tumors (i.e., tumors with signet ring cells that lack tubular formation) must be distinguished from ovarian tumors that contain signet ring cells with mucinous or nonmucinous material.

Ovarian tumors with mucin stain similar to Krukenberg tumor, but they also stain positive for chromogranin and synaptophysin which can differentiate them from Krukenberg tumor.

Ovarian tumor with signet ring cell without mucin are divided into signet-ring stromal tumor (benign, unilateral, devoid of epithelial differentiation, stain positive for vimentin and negative for cytokeratin), sclerosing stromal cell tumor (contain lipid with no reactivity to periodic acid-Schiff stain and stain positive for inhibin stain), and clear cell adenocarcinoma of the ovary (contains glycogen that stains with periodic acid-Schiff, papillary and tubulocystic pattern with hobnail cells).

Tubular Krukenberg tumors (i.e., cells arranged in tubules) must be distinguished from ovarian tumors with an annular or tubular pattern including Sertoli-Leydig cell tumor (lack of signet-ring cells, stain positive for inhibin and negative to cytokeratin), endometrioid carcinoma, and tumor of Wolffian origin[1][2].


Since Krukenberg tumor is a metastatic disease from the gastrointestinal site or other organs, it is classified as stage IV disease.


Given the bilateral and metastatic nature of this disease, prognosis remains poor. Patients usually die in 2 years with a median survival of 14 months reported in the literature. The median overall survival of patients with Krukenberg tumor is reportedly 11, 21.5, 31, and 19.5 months for gastric, colorectal, breath, and other origins respectively[9][10].

Pearls and Other Issues

Krukenberg tumor is a metastatic disease to the ovaries composed of mucin-rich signet-ring cells. The most common primary site for this tumor is the stomach. These tumors spread most likely through the lymphatic channels. Diagnosis of Krukenberg tumor involves careful radiological evaluation of gastrointestinal and other potential sites. With a known primary tumor, CA-125 levels can help with early detection of ovarian metastasis as well assist with prognosis and monitoring of this disease. Currently, no established treatment is available with extremely poor prognosis for this tumor.

Enhancing Healthcare Team Outcomes

The diagnosis and management of krukenberg tumor is complex and should involve an interprofessional team that includes hospice, palliative care nurse, pain specialist, oncologist, surgeon, pathologist, and radiologist. In all cases, this is metastatic disease and the patients are frail and debilitated. Aggressive surgery is not recommended as it does not extend life span. Most patients may benefit from hospice care and pain control. The majority of patients are dead within 12-24 months with or without treatment.[7] [8](level V)

Article Details

Article Author

Muhammad Aziz

Article Editor:

Anup Kasi


1/22/2021 9:51:12 PM

PubMed Link:

Krukenberg Tumor



The pathogenesis, diagnosis, and management of metastatic tumors to the ovary: a comprehensive review., Kubeček O,Laco J,Špaček J,Petera J,Kopecký J,Kubečková A,Filip S,, Clinical & experimental metastasis, 2017 Jun     [PubMed PMID: 28730323]


An in-depth look at Krukenberg tumor: an overview., Al-Agha OM,Nicastri AD,, Archives of pathology & laboratory medicine, 2006 Nov     [PubMed PMID: 17076540]


Bennett JA,Oliva E, Pathology of the adnexal mass. Clinical obstetrics and gynecology. 2015 Mar;     [PubMed PMID: 25608250]


Crăciun MI,Domşa I, Immunohistochemical diagnosis of Krukenberg tumors. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2017;     [PubMed PMID: 29250663]


Transcoelomic spread and ovarian seeding during ovulation: A possible pathogenesis of Krukenberg tumor., Shah B,Tang WH,Karn S,, Journal of cancer research and therapeutics, 2017 Jan-Mar     [PubMed PMID: 28508852]


Sigmoid colonic metastasis by lymphatic spread occurring with unilateral Krukenberg tumor considered to be caused by stage IA early gastric cancer: A case report., Fujimoto D,Hirono Y,Goi T,Yamaguchi A,, Oncology letters, 2016 Jan     [PubMed PMID: 26870264]


Agnes A,Biondi A,Ricci R,Gallotta V,D'Ugo D,Persiani R, Krukenberg tumors: Seed, route and soil. Surgical oncology. 2017 Dec;     [PubMed PMID: 29113663]


Seow-En I,Hwarng G,Tan GHC,Ho LML,Teo MCC, Palliative surgery for Krukenberg tumors - 12-year experience and review of the literature. World journal of clinical oncology. 2018 Feb 10;     [PubMed PMID: 29468133]


Wu F,Zhao X,Mi B,Feng LU,Yuan NA,Lei F,Li M,Zhao X, Clinical characteristics and prognostic analysis of Krukenberg tumor. Molecular and clinical oncology. 2015 Nov;     [PubMed PMID: 26807242]


Tan KL,Tan WS,Lim JF,Eu KW, Krukenberg tumors of colorectal origin: a dismal outcome--experience of a tertiary center. International journal of colorectal disease. 2010 Feb;     [PubMed PMID: 19705132]