Krukenberg tumors are rare cases of metastatic ovarian tumors. Generally, they are bilateral and 70% originate in the stomach, but they can also originate in other organs. They are normally found in young women, on average at 45 years of age, and normally present symptoms due to ovarian involvement: abdominal pain, bloating, nonspecific gastrointestinal symptoms or ascites with malignant cells. They can also be asymptomatic. The diagnosis of the primary tumor can be made before surgery, during further investigations, or during the months following operative surgery. CT and MRI allow the diagnosis and the follow up. The best exam is surely the PET-CT to evaluate an extension (metastasis). Post-surgical and post-therapeutic monitoring is provided by these images. The primary tumor is often too small to be detected and diagnosis depends on meticulous radioscopic and endoscopic exploration. They're usually found in young women. Our two cases imposed a difficult discovery but a good survival for both.
2. Reported Cases
We were able to identify two cases of Krukenberg tumor in Fribourg,
Cantonal hospital, during 2016, and we carried out a review of the existing
literature about Krukenberg tumors.
3.1. First Case
Mrs. R.D., 62 years old, 2G2P, who presented with abdominal cramps along
with constipation and a weight loss of 7 kg. The endoscopic and radiological exams
both concluded with the diagnosis of adenocarcinoma. The patient underwent a
left hemi colectomy with sigmoid resection, Complete Mesocolic Excision (CME)
and side-to-end anastomosis two months later. The definitive anatomo-pathology report
showed a moderately differentiated adenocarcinoma, ulcerated and stenosing,
with an infiltration of all the layers of the colic wall, multifocal overtaking
of the serosa, and venous and perineural infiltration (tumor size 3 cm), 3
positive lymph nodes out of 20. No notion of microsatellite instability on the
immunohistochemistry. The final TNM UICC 2009 classification was pT4a N1 (3/20)
V1 Pn1 R0 (axial sections) G2. The patient was next treated with an adjuvant chemotherapy
of 10 doses of FOLFOX (5-FU and Eloxatine) and 2 doses of 5-FU and Leucovorin for
6 months. The follow-up CT-scan, about one year after the primary surgery,
showed a massive cystic mass of 125 x 130 x 160 mm, with septations, on the
ovary with suspect lesions on the spleen and the liver (Figures
The CEA was 7.3 ng/ml, the CA 125 was 200 U/ml, the CA 15-3 was 18.6
U/ml, the CA 19-9 was 30 U/ml and the AFP was 1.3 ng/ml. The patient underwent a
bilateral adnexectomy, a total hysterectomy, the ablation of a 19 cm annexial
mass with omentectomy, appendectomy, splenectomy, resection of hepatic metastasis
of segment VI and peritoneal washing under the care of the gynecology and
surgical teams. Postoperative period care was uneventful. The definitive
histology was positive for bilateral ovarian metastasis with uterine
infiltration of a stenosing adenocarcinoma of the descendant colon. The
peritoneal washing was negative. The case was presented at the Tumorboard,
which proposed a palliative chemotherapy with Erbitux and FOLFIRI and the follow-up
thoraco-abdominal CT-scan of 02.01.2017 did not show any evidence of new
3.2. Second Case
Mrs. R.L., 52 years old, 2G2P, menopaused for 2 years,
who initially presented with epigastralgia with no sign of improvement despite
an appropriate treatment. The endoscopic examinations as well as the biopsies were
negative. The radiologic exam with MRI showed two ovarian masses of 10 and 14
cm of diameter (Figure 4), with heterogeneous
hypercaptation on the PET-CT (Figure 5).
For the tumoral markers, the CA 19-9 was 236 U/ml, the
CA 125 was 149 U/ml and the CA 15-3 was 11-6 U/ml. The patient underwent a median
laparotomy, which showed massive ascite, a caecal and right colic dilatation on
the anterior face with a stenosis of the right external third of the transverse
colon and the presence of a gastric linitis with retroperitoneal infiltration
of the entire susmesocolic space. The pelvis contained two solid masses, each
of 12 cm of diameter. A bilateral adnexectomy, a total hysterectomy and a right
hemicolectomy were performed. Postoperative period care was uneventful.
The cytology of the ascites showed atypical cells,
malignant, of an undifferentiated adenocarcinoma. An immuno-histochemical study
was made, but the origin of the cells could not be identified on the sample.
The definitive histology showed an adenocarcinoma, mostly with signet ring
cells, with bilateral infiltration of the ovaries, infiltration of the colic
wall, peritoneal carcinosis and vascular, lymphatic and perineural invasion; 15
out of 21 lymph nodes were positive. The final diagnosis was a gastric cancer,
type adenocarcinoma, stage IV, with ovarian metastasis. The Tumorboard proposed
chemotherapy mDCF (Taxotere, 5-FU, Platinol) for which the patient had a
portacath inserted. The treatment was well tolerated by the patient and a new
PET-CT didn't show any suspicious lesions.
4. Literature Analysis
are unusual metastatic tumors of the ovaries first described by Friedrich
Krukenberg, a German gynecologist and pathologist, in 1896. In 1902
Schlagenhaufer emphasized that these ovarian tumors do not originate in the
ovary, but are metastases from a primary malignancy somewhere else. Moreover,
Schlagenhaufer stated that the most common primary site is the gastrointestinal
Nowadays, the term ‘‘Krukenberg tumor’’ indicates any
ovarian metastatic carcinoma deriving from a primary malignancy. However, the
World Health Organization’s diagnostic criteria states that a diagnosis of a Krukenberg
tumor is based on the presence of stromal involvement, mucin-producing
neoplastic Signet Ring Cells (SRCC) and ovarian stromal sarcomatoid
From 2008 to 2012, an incidence of 584 cases of
ovarian cancer was seen in Switzerland, which accounts for 3.3% of all new
cases of cancer. The mortality of those tumors is high during the same period,
with 425 deaths, which means 5.9% of all cancer deaths. The incidence is the
same as the one found in central Europe or in North America .
Metastatic tumors among ovarian carcinomas are rare
(about 7%) and Krukenberg tumors represent only 1-2% of all ovarian tumors [1,3]. The signs in favor of metastasis are
bilateralism (74% of the cases are bilateral), size of the lesion, involvement
of the surface and important intra-abdominal extension .
The women who suffer from Krukenberg tumors are particularly young, with an average
age of 45 years .
The stomach is the main primary site of Krukenberg
tumors, and represents 70% of the cases, as in our 2nd case study; for this reason, the frequency of
those tumors in different countries varies along with the one of gastric
carcinoma . The next more frequent
localizations are colon (as in our 1st
case study), appendix and breast (most invasive lobular carcinomas). Rarely,
cases are described coming from the biliary tract, the pancreas, the small
intestine, the ampulla of Vater, the cervix and the bladder. Sometimes, the
primary tumor is very small and can escape detection, which is the case in our
second patient .
Two different sorts of metastasis can be described: synchronous
metastases, which are discovered simultaneously with the primary tumor, and
metachronous, more frequent, discovered after the primary tumor . The ovaries are the second most frequent sites of
metastasis of gastrointestinal tumors, after the liver. The route of metastasis
is a controversial mechanism. The most probable hypothesis is that the
malignant cells follow a retrograde lymphatic trajectory, a hypothesis supported
by microscopic evidence on the lymphatic capillaries, by the initial
involvement of the gastric mucosa and the submucosa (rich in lymphatic
capillaries) and by some studies that showed a higher risk of ovarian
metastasis when more lymph nodes are involved. Moreover, the theory of
extension through the peritoneum is minimized because of the frequent lack of
tumor cells on the peritoneum and the absence of implants on the surface of the
A lot of patients initially present with symptoms of
the metastases instead of those of the primary tumor .
They are mainly abdominal bloating with a sensation of discomfort, weight loss,
dyspnea, abdominal pain, some nausea or vomiting or epigastric pain. Most
patients present non-specific gastrointestinal symptoms or are asymptomatic.
A virilization can also be present, because of the
hormonal production of the ovarian stroma. In 50% of cases, ascite is seen with
frequent presence of some malignant cells .
The clinical exam can reveal an abdominal or pelvic
In our two cases, the patients are rather young,
respectively 52 and 62 years old. The symptoms are also in both cases
non-specific. In the first case, there were no symptoms and in the second case,
only some gastrointestinal symptoms with epigastralgia, which can come from the
gastric carcinoma itself and with ascite discovered per-operatively, that
contained malignant cells.
Sonography is a good method for the initial evaluation
of ovarian neoplasms. CT does not increase the diagnostic accuracy, but can show
the extent of the disease, better evaluate the gastrointestinal tract, evaluate
recurrent carcinoma and follow the response to treatment.
When a CT is performed as a preoperative evaluation of
gastric or colon carcinoma, the ovaries should also be looked at for possible
Krukenberg tumor. On CT, Krukenberg tumors typically look like an oval or
kidney-shaped mass, with preservation of the ovary contour. Usually, they’re
solid or predominantly solid with central necrosis and with an enhancement of
solid components or septations after contrast media administration. They can
also look like large lobulated cystic masses. Unilateral involvement may be
seen, with a normal contralateral ovary, but most of the time the lesions are
On MRI, Krukenberg tumors have either low or high
signal intensity on T2-weighted images because they can have abundant collagen
formation or marked oedema. They appear normally as complex masses with
hypo-intense solid components, with some hyperintensity on T1 and T2-weighted
MR images. The wall of the cyst usually shows contrast enhancement  (Figures 1,3,4).
It can be difficult or impossible to make a clear
distinction between primary and metastatic ovarian cancers [8,9]. However, a bilateral, sharply delineated, predominantly
solid lesion with necrosis suggests metastasis [10,11]
3.6 In many cases, the CA 125 is higher in the
patients with a Krukenberg tumor, and it decreases after surgery. Thus, it is
possible to use this marker for follow-up after a complete resection of the tumor,
also for the follow-up of patients known to have an adenocarinoma of the
gastrointestinal tract in order to detect an ovarian involvement early .
In our two patients, the CA 125 was high, 149 and 200
U/ml respectively. Those values represent a poor prognosis; indeed, the 5-years
survival rate is decreased in patients with a postoperative CA 125 level above
75 U/ml .
Theoretically, systemic chemotherapy is the optimal
treatment for recurrent or metastatic gastric cancer. However, in the case of Krukenberg
tumors, this modality doesn’t show any significant survival benefit because the
medication normally used for gastrointestinal tract carcinomas has a low
anti-neoplasic activity in the ovaries, which represent a sanctuary for the
cancer cells . Likewise, a metastasectomy is
not clearly beneficial for this precise case. It is also to be noted that as a
lot of Krukenberg tumors are metachronous, many patients have already been
treated by chemotherapy before the metastasis appears. Presently, we don’t have
a clear treatment protocol for those tumors.
A Korean study from 2014 
compared the survival benefit of the possible treatments for Krukenberg tumors.
The results show that regardless of tumor stage, the patients with complete resection
of metastasis and chemotherapy have a better survival rate than those with chemotherapy
only. Surgery however is controversial because of the poor prognosis, the bad
tolerance of the patients to the surgery, the bad resectability rate and the
high risk of surgical complications . In
patients with unilateral metastasis and surgical resection, the unaffected
ovary should always be removed, because it has the same probability to be
reached by the cancer cells and could already contain micro-metastases. Most
authors also suggest that bilateral oophorectomy is prophylactically indicated
at the time of colon resection .
For now, we only have a restricted vision on our cases follow-up, given
the recent date of their occurrence. However, the two patients are now under adjuvant
chemotherapy, with absence of lesion recurrence on control CT-scan Krukenberg
tumors generally have a poor prognosis, with death of most of the patients in
the 2 years after the diagnosis has been made (median survival is 14 months) . Furthermore, the prognosis is worse for patients
in whom the primary tumor is discovered after the metastasis and even worse if
the primary tumor stays unidentified. The presence of other metastases after the
ovary is also a sign of a poor prognosis .
In both cases of Krukenberg tumors that we treated at HFR-Fribourg
during 2016, both originated from the gastrointestinal tract, one from the
stomach and the other one from the colon, initially at an advanced stage and finally
a palliative stage. These tumors are rare, but it's very important to be able
to recognize them and to treat them early because of their bad prognosis. The
difficulty is that this disease is rare, and it can take a lot of time to make
the diagnosis, which is made with the help of radiologic and other
complementary investigations. For now, the best treatment to improve prognosis
seems to be surgery, in addition to a multidisciplinary oncological approach.
7. Ethics Statements
Written informed consent was obtained from the patient prior to
presenting the two cases. No ethical problem and no conflict of interest.
8. Author Contributions
Each of the authors (MC, MB, NBA, TO, AF, JBJ and FK) participated in
caring for the patient. MC is the principal author.
Figure 1: Follow-up CT-scan - appearance of a huge pelvic mass.
Figure 2: PET-CT 18-FDG-pelvic mass, hyperactive lesions in the liver and the
Figure 3: MRI sagittal view T2 (up) and
axial view T2 (down).
Figure 4: MRI sagittal view T2 (left),
axial view T2 (right).
Figure 5: PET-CT 18-FDG heterogenous
hypercaptation of the pelvic tumor.
Citation: Crisinel M, Boukrid M, Feki A, de la Jolinière JB (2018) Krukenberg Tumors: Two Cases Report and A Literature Review. J Surg 2018: 1169. DOI: 10.29011/2575-9760.001169