Krukenberg Tumors: A Review - Progressive Science


Krukenberg Tumors: A Review - Progressive Science
doi: 10.14721/pscience.2015.e12
Krukenberg Tumors: A Review
Talia K. Ben-Jacob, Chad R. Gordon, Frank Koniges
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, Cooper University Hospital | Camden, New Jersey, USA.
elevated at 13 and 882, respectively, and her hemoglobin was low at
10.9. Her electrolytes were all within normal limits and her urinalysis
was positive for a urinary tract infection. An obstruction series was
performed that revealed a laterally-displaced, dilated loop of colon in
the left lower quadrant (Figure 1).
The patient was admitted to the general medicine service, with
consults placed to the gastroenterology, general surgery, and
gynecology-oncology services. A computed tomography (CT) scan
of her abdomen/pelvis demonstrated a large pelvic mass of unknown
etiology (Figure 2). The mass was displacing her small bowel in the
cephalad direction and partially obstructing her left ureter, with bi-lobar
liver lesions suspicious for metastasis. A colonoscopy revealed a nearobstructing colon lesion reported to be at 60 cm from the anal verge.
Biopsies were obtained and consistent with colonic adenocarcinoma.
She underwent an exploratory laparotomy, with plans for a diverting
ileostomy or colostomy and mass biopsy.
Exploratory laparotomy revealed two large, complex ovarian
masses. The right ovary was easily mobilized and resected. The ovary
measured 25 x 23 x 8 cm and weighed 2,500 grams (Figure 3). The
left ovary was also massive, but unlike the other, was adherent to the
patient’s sigmoid colon and pelvic sidewall. After careful dissection,
A Krukenberg tumor is a rare tumor of the ovary derived from
metastatic gastrointestinal tissue. Although the eponym is
attributed to Dr. Friedrich Krukenberg, a German gynecologist and
pathologist, the Krukenberg tumor was actually described by both
Paget (1854) and Wilks (1859). Worldwide, they account for about
1% of all ovarian neoplasms. Gastric cancer is the most frequent
primary source, followed by breast, colon and appendix. For
those carcinomas originating from the intestinal tract, about 80%
are found within either the sigmoid colon or rectum. Presenting
symptoms include nonspecific abdominal pain, distention, ascites,
virilization, hirsutism and menometrorrhagia. This paper presents
the hospital course and operative intervention on a 48-year-old
female with bilateral ovarian Krukenberg tumors metastasized
from an adenocarcinoma of the sigmoid colon.
Citation: Ben-Jacob TK, Gordon CR, Koniges F (2015) Prog Science 2(2):e12 |
doi: 10.14721/pscience.2015.e12
Original Published: J Surg Radiol. 2010 Jul 1;1(1) | Republished: 02/20/2015
Copyright: © 2015 Ben-Jacob TK. et al. Published by TranScience. This is an open
access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
Funding: none
Competing Interests: The authors have declared that no competing interests exist.
E-mail: [email protected]
A 48 year old female presented to the emergency room with vague
abdominal discomfort, nausea/vomiting, abdominal distention,
constipation, pencil-thin stools, and recent weight loss. Her family
history was not significant for malignancy, and her social history
included a remote 20 pack year smoking history. She had been
admitted three weeks prior to the gynecology/oncology service for
menometrorrhagia and suspected gynecologic cancer. She had a
cervical biopsy suspicious for cervical carcinoma, and was then
discharged home to follow up with medical oncology and gynecology/
oncology as an outpatient.
On physical exam, the patient was alert and oriented, tachycardic,
and with decreased breath sounds in the lower lung bases. Her
abdomen was soft but distended by a large palpable, hard mass
and significant ascites. Her rectal exam was non-tender, hemoccult
positive with no masses appreciated. Edema was noted bilaterally in
her lower extremities. At this time, she underwent a paracentesis in the
emergency room for symptomatic relief and approximately 4.5 liters
of peritoneal fluid were removed. Her fluid was sent for analysis and
contained the following: protein 3.3, RBC 630, and WBC 650 (with
12% segmented neutrophils). Her serum WBC and platelets were
Progressive Science |
Figure 1 | X-ray showing a displaced, dilated loop of large bowel in
the left lower quadrant.
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Ben-Jacob et al.
Case Report | Krukenberg Tumors
the left ovarian mass was removed and measured 24 x 20 x 9 cm
and weighed 1,760 grams (Figure 4). The attached sigmoid colon was
inspected and found to contain the obstructing cancer found during the
previous colonoscopy (Figure 5).
Further inspection revealed peritoneal studding and liver nodules.
There was also “tumor-caking” found periodically along the small
bowel mesentery and greater omentum without any evidence of bowel
invasion. After the bilateral salpingo-oopherectomy, the sigmoid
colon was resected and a hand-sewn end-to-end anastomosis was
Final pathology concluded that both ovaries and tubes had been
completely replaced by metastatic colonic adenocarcinoma. The
sigmoid colon contained a 4.5 cm tumor consistent with moderatelydifferentiated, infiltrating colonic adenocarcinoma, invading through
the muscularis propria into the subserosa. There was extensive
lymphovascular invasion and 5/10 lymph nodes were positive. The
patient was pathologically staged as a T3N2M1. The colonic primary
and metastatic ovarian lesions underwent microscopic review and
immunohistochemical staining. It was demonstrated that the masses
had very similar morphology and an identical immunohistochemical
profile (cytokeratin 20-positive, cytokeratin 7-negative). With these
findings, the cancer was determined to be of colonic origin with
metastases to the cervix, liver, and ovaries.
Fortunately, the patient did very well post-operatively. She was
uneventfully advanced to a regular diet and was discharged home on
post-operative day five, with plans to follow-up with the surgeon and
the medical oncology service as an outpatient.
Figure 2 | CT scan demonstrating a large pelvic mass.
diagnosis, with a median 5-year survival of 14 months.3 The prognosis
is poor if the primary tumor is identified after ovarian metastasis has
occurred, and even worse if the primary is unidentified.5
Metastatic adenocarcinoma to the uterine cervix from the
gastrointestinal tract is rare and very few cases are reported. The route
of metastasis to the cervix is surmised to be retrograde via lymphatics,
similar to the pathway of metastases to the ovary.6 Cervical metastasis
may often be the presenting symptom, discovered either synchronously
or after the diagnosis of gastro-intestinal carcinoma has been made.
Unfortunately, for this subset of Krukenberg tumor patients, their
diagnosis is poor no matter when their cervical metastasis is identified.6
Gross findings of a Krukenberg tumor-containing ovary include
asymmetrical enlargement, lobular contour, and either solid or cystic
consistency. Commonly, the ovaries are spared from intra-peritoneal
adhesions and present without any peritoneal deposits.3 Kiyokawa et
al. reported that Krukenberg tumors can range in texture from firm
and solid to edematous and gelatinous, with only approximately 30%
containing cysts. They also found the mean size to be 10.4 cm.4
Microscopically, the Krukenberg tumor is composed of mucinladen signet-ring cells and ovarian stromal cells. Krukenberg tumors
can either display a prominent tubular pattern or one that is clustered.
Lobular patterns, with nodules separated by stroma, can also be seen.
Mucin-laden signet ring cells are essential for the diagnosis of a
Krukenberg tumor.3 However, sometimes the desmoplastic reaction
of the stromal cells can be so severe that it obscures the signetring pattern. The literature describes great variation in the different
cellular atypia. The stroma can range from cellular to paucicellular
and from edematous to mucoid. The degree of signet-ring cell
prominence also varies from case to case.4 The overall morphology
of the adenocarcinoma is graded based on the presence of mucin,
edema, stromal patterns and the number of signet-cells. Often it is
difficult to differentiate between primary and metastatic ovarian
carcinoma. Careful attention must be paid to the microscopic finding
of invasion and implantation to distinguish the two metastatic modes.1
Based on 120 Krukenberg tumor cases, Kiyokawa determined that
The Krukenberg tumor was originally described by Paget (1854).1
The eponym is attributed to Dr. Friedrich Krukenberg, a German
gynecologist and pathologist. In 1896, he published five case reports
on what he believed to be at the time a new type of ovarian tumor.
However, in 1902, Dr. Schlagenhauffer determined that these tumors
were in fact of metastatic gastrointestinal tract origin.2
Krukenberg tumors are pathologically “signet ring cell” ovarian
adenocarcinoma. They account for 1-2% of all ovarian tumors worldwide.3 In Japan, their prevalence is greatly increased to almost 20%
(due to the increased prevalence of gastric cancer).3 The stomach is
the primary site in 70% of these cases, followed by breast, colon, and
appendix, in that order.1 For those tumors originating from the intestinal
tract, 80% are found to be within the sigmoid colon or rectum.1
Unfortunately, these primary colonic tumors are often too small for
endoscopic detection (i.e. colonoscopy), thereby necessitating either
CT scan or ultrasound.
Women are typically diagnosed with Krukenberg tumors in the
perimenopausal fifth decade of life, with the average age of diagnosis
being 45 years-old. It is hypothesized that this young age of diagnosis
is related to the great vascularity of their ovaries, which facilitates
vascular metastasis.1 It is interesting to note that for those patients
with Krukenberg tumors originating from the colon, the mean age of
presentation is subsequently delayed. Presenting symptoms usually
include, but are not limited to, vague abdominal pain, distention, and/
or ascites. Occasionally, abnormal vaginal bleeding, virilization and
hirsutism can be seen.4
Krukenberg tumors are bilateral in 80% of cases.3 The route of
metastasis from the gastrointestinal tract to the ovaries is hypothesized
to be via lymphatics. The mortality rate for Krukenberg tumors is
relatively high and a majority of patients die within two years of
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Ben-Jacob et al.
Case Report | Krukenberg Tumors
the histological spectrum is much more diverse than what has been
previously reported.4
In these aforementioned cases, special diagnostic stains can be
used to highlight the presence of signet cells. Immunohistochemistry
can also be used to decipher metastatic carcinoma from primary
ovarian neoplasms.1 The ovarian tumors that are immunoreactive
to CEA, stain positive for cytokeratin 20 (CK20) and negative for
cytokeratin 7 (CK7), are more likely to be of colorectal origin and
increase the pathologist’s confidence in making the diagnosis of a
Krukenberg tumor.3 This differs from primary ovarian tumors, since
they usually test positive for CK 7 and negative for CK 20. Other
immunohistochemicals currently under investigation include CD44v6,
vascular endothelial growth factor, and matrix metalloproteinases
2 and 9 (MMP-2 and MMP-9). Lou et al. compared 35 cases of
Krukenberg tumor to normal tissue and found that the expression rate
of CD44v6, VEGF, MMP-2 and MMP-9 were significantly higher
in those with Krukenberg tumors.7 However, these factors were
also found within primary epithelial ovarian carcinomas and were
therefore not exclusive to Krukenberg tumors.5 CA-125 is a tumor
marker elevated in patients with Krukenberg tumors and usually
found to decrease after resection. Therefore CA-125 can be used
either for post-operative follow up and/or for patients with a history of
adenocarcinoma with no identifiable ovarian metastasis.3
There is currently no optimal or curative treatment strategy for
Krukenberg tumors. Surgical resection has only been shown to be
effective in patients with limited metastasis confined to the ovaries.3
Patients often experience recurrence after curative surgery thereby
preventing them from receiving further treatment. For these types of
patients, Cheong et al. investigated the role of metastectomy for the
management of metachronous tumors following curative surgery. Their
study found the median survival for patients undergoing metastatic
resection was significantly increased versus the non-resection control
group (17 months vs. 3 months).5 Further investigation is warranted to
decide the optimal role of surgery in patients with Krukenberg tumors.
Figure 3 | Right Fallopian tube and ovary.
Figure 4 | Left Fallopian tube and ovary.
Young RH. From Krukenberg to Today: the ever present problems posed by metastatic
tumors in the ovary. Part 1: historical perspective, general principles, mucinous tumors
including the Krukenberg tumor. Adv in Anat Path 2006; 13(5):205-27.
Onuigbo WIB. Early descriptions of Krukenberg tumors. J Amer Coll Surg 2005;
Al-Agha OM and Nicastri AD. An in-depth look at Krukenberg tumor. Arch Path and
Lab Med 2006; 130:1725-30.
Kiyokawa T, Young RH and Scully RE. Krukenberg Tumors of the Ovary: A
clinicopathologic analysis of 120 cases with emphasis on their variable pathologic
manifestations. Amer J of Surg Path 2006; 30(3):277-99.
Cheong JH, Hyung WJ, Chen J, Kim J, Choi SH and Noh SH. Survival benefit of
mastectomy for Krukenberg tumors from gastric cancer. Gyn Onc 2004; 94:477-82.
Imachi M, Tsukamoto N, Amagase H, Shigematsu T, Amada S, Nakano H. Metastatic
adenocarcinoma to the uterine cervix from gastric cancer. A clinicopathologic analysis
of 16 cases. Cancer. 1993: 71(11):3472-7.
Lou G, Gao Y, Ning XM and Zhang QF. Expression and correlation of CD44v6, vascular
endothelial growth factor, matrix-metalloproteinase-2, and matrix-metalloproteinase-9
in Krukenberg tumor. World J of Gastroent 2005; 11(32):5032-36.
Figure 5 | Sigmoid colon with obstructing cancer.
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