INTERNATIONAL JOURNAL OF CLINICAL INVESTIGATION AND CASE REPORTS - Volume 1, Issue 1, (May-July)
Pages: 23-28
Date of Publication: 15-Jul-2022
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Krukenberg Tumor Secondary to Pancreatic Ductal Adenocarcinoma: A Case Report
Author: Samantha Sosa, Layla L. Monroy, Manuel Lavariega, Jose M. Portela, Rogelio A. Sanchez, Armando Lopez, Maria T. Bourlon, Sergio Sanchez, Alejandro Rossano* (MEXICO)
Category: Surgery
Abstract:
Background: A metastatic tumor of the ovary known as Krukenburg Tumor (KT) is a mucin-rich signet-ring adenocarcinoma that arises from a gastrointestinal site in most cases and from other sites in less proportion. We describe a rare case presenting a Krukenberg tumor secondary to pancreatic ductal adenocarcinoma.
Case Presentation: A 51-year-old female, who started her current condition 6 months ago, with 15 kg of weight loss, accompanied by nausea, vomiting, early satiety, and constipation. Computerized tomography showed dependent mass involving the body and tail of the pancreas with solid and cystic components, highly suggestive of a primary tumor as well as peritoneal carcinomatosis and a left ovarian mass, tumor (Krukenberg) as a first possibility. A laparoscopy was performed. The final pathology report was a pancreatic ductal adenocarcinoma with metastases to the ovary from the left salpingectomy.
Conclusion: Pancreatic cancer presenting as Krukenberg tumor of the ovary is rare and easily misdiagnosed as primary ovary carcinomas, which leads to missed surgical opportunities. Resection of ovarian metastases combined with chemotherapy treatment may increase the overall survival even in patients with advanced pancreatic ductal adenocarcinoma.
Keywords: Krukenberg Tumor, Metastases, Ductal Pancreatic Adenocarcinoma , Ovary Adenocarcinoma, Neoplasm Metástasis , Ovarian Neoplasms
DOI: 10.55828/ijcicr-11-05
DOI URL: http://dx.doi.org/10.55828/ijcicr-11-05
Full Text:
INTRODUCTION
A metastatic tumor of the ovary known as Krukenburg Tumor (KT) is a mucin-rich signet-ring adenocarcinoma that arises from a gastrointestinal site in most cases and from other sites in less proportion. Friedrich Ernst Krukenberg first described five cases of this ovarian malignancy in 1896, the tumor was named after him. KTs make up about 1% to 2%, of all diagnosed ovarian tumors [1,2]. The primary site in about 70% of cases is the stomach. Almost 90% of the primary sites for this tumor are colorectal and gastric cancers collectively. Other primary sites are the small intestine breast, biliary tract, gallbladder, ampulla of Vater, appendix, pancreas, urinary bladder, or cervix [1]. Primary pancreatic adenocarcinoma is identified in 5% to 14% of all Krukenberg tumors of the ovary [3, 4]. Pancreatic carcinoma that has metastasized to the ovaries is diagnosed in 2% to 19% of patients. The main differential diagnosis is the primary ovarian mucinous carcinoma because pancreatic adenocarcinoma can produce large multicystic tumors that have similarities with primary ovarian mucinous neoplasms [5]. Many pancreatic and ovarian carcinomas are positive for CK7 and show variable expression of CK20. Krukenberg tumors are negative for hormone receptor expression (progesterone and estrogen receptors), unlike primary mucinous neoplasms of the ovary. The World Health Organization diagnostic criteria for KT are based on the pathologic description by Serov et al. [2]. The following features are required for the diagnosis of KT: ovarian stromal infiltration by poorly differentiated adenocarcinoma, presence of mucin-secreting neoplastic signet ring cells, and ovarian stromal sarcomatoid proliferation. Primary and secondary ovarian malignancies do not have significant differences in symptoms. KT remains asymptomatic until advanced stages. The patient presents non-specific features, like weight loss increasing abdominal girth as well as abdominal pain [6, 7].
CASE PRESENTATION
A 51-year-old female presented with 6 months history of weight loss, nausea, vomiting, early satiety, constipation, anorexia, abdominal distention, and asthenia. The patient's family history was positive for gastric adenocarcinoma (no need for family history part again). On examination, the patient appeared to be distended with large volume abdominal ascites, which tested positive for malignant cells. She was found to have hypochromic microcytic anemia with 4.9 hemoglobin. Additional workup showed elevated liver function tests with a hepatocellular pattern, elevated CA 19-9 (most widely used tumor marker in pancreatic cancer), and CA 125 (tumor marker which is commonly expressed by the epithelial ovarian neoplasms). Abdominal CT (Figure 1 and Figure 2) revealed a pancreatic mass, with solid and cystic components, involving both the body and tail of the pancreas. Additionally, imaging showed a left ovarian tumor and peritoneal carcinomatosis. Subsequent laparoscopy demonstrated left ovarian mass (Figure 3) with solid and cystic components, peritoneal implants including the mesoappendix, and liver metastases.
The pathology revealed moderately differentiated ductal pancreatic adenocarcinoma metastatic to the liver, peritoneum, and ovary as well as a synchronous mucinous cystadenoma of the ovary. Hospitalization was further complicated by small bowel obstruction at the third portion of the duodenum, requiring gastrojejunal bypass as well as a cecal mass (Figure 4) which was also revealed to be metastatic pancreatic adenocarcinoma. Following surgical management, chemotherapy with FOLFOX was initiated.

Figure 1: Contrast-enhanced computed tomography of the thorax, abdomen, and pelvis, showing heterogeneous liver parenchyma, pancreatic mass involving the body and tail of the pancreas with solid and cystic components, lobulated left ovarian tumor with hypodense content, and internal septations.

Figure 2: Contrast-enhanced computed tomography, axial slice showing tumor in the left ovary, probable Krukenberg.

Figure 3: Laparoscopy showed a complex tumor of the left ovary.

Figure 4: Cecal tumor obstructing the bowel lumen, demonstrated on colonoscopy.
Final Diagnosis
Grossly, the left ovary was enlarged at 5.7 cm x 5.5 cm, with a lobulated, smooth surface. Sectioning revealed a multicystic tumor containing mucinous secretions. Pathology revealed variably sized glands, with abundant mucinous cytoplasm, infiltrating the ovarian stroma. The neoplastic glands exhibited CK7+/CK20- immunophenotype, which accounts for 75% of pancreatic adenocarcinomas. Negative staining for CK20 favored pancreatic metastasis over a primary mucinous neoplasm of the ovary, which tends to show patchy staining for CK20. However, as stated above both ovarian and pancreatic adenocarcinoma can show variable expressions of CK20, leading to overlapping immunoprofiles (Figure 5).
The presence of a main pancreatic mass, relatively small size of the ovarian tumor (<10 cm), stromal infiltration, and positive staining for ductal marker CK19 pointed toward a KT originating from the pancreas, with metastases to the ovary, peritoneum, liver, and appendix (Figure 6 and Figure 7).

Figure 5: Ovarian stroma with metastasis of moderately differentiated adenocarcinoma mixed with a mucinous cystadenoma.

Figure 6: Variably sized, neoplastic glands showing immunoreactivity for CK7.

Figure 7: Negative staining for CK20, favoring pancreatic metastasis over a primary mucinous neoplasm of the ovary.
It was determined after the first surgery that the patient was in the IV clinical stage of pancreatic cancer, she was offered supportive treatment with chemotherapy to reduce tumor activity and a gastro-jejunal bypass to solve intestinal obstruction and improve her quality of life.
Treatment
The patient underwent left salpingo-oophorectomy, appendectomy, resection of liver metastases, and peritoneal implants, followed by systemic chemotherapy with FOLFOX.
Outcome and Follow Up
Two months later, the systemic chemotherapy for the pancreatic adenocarcinoma with FOLFOX is still being continued and the patient is asymptomatic with a normal CA 19-9, free from Krukenberg tumor recurrence.
DISCUSSION
Krukenberg tumors, constitute 1% to 2% of all diagnosed ovarian tumors. It can rarely present as a unilateral ovarian mass as in our patient, although 80% of the cases have been reported to be bilateral [1]. Pancreatic adenocarcinoma as primary cancer has seldom been reported, accounting for 5% to 14% of all ovarian metástasis [3,4].
The metastatic mucinous carcinomas tend to be bilateral, with ovarian surface involvement as well as extra ovarian disease as in our case with extensive metastases involving the peritoneum, liver, and colon [7]. KTs often show nodular growth patterns and infiltrative stromal invasion; whereas primary ovarian mucinous tumors are unilateral, relatively larger, with solid and cystic components, smooth surface, and are not associated with extra ovarian disease [3].
Ovarian tumors usually dominate the clinical presentation with lower abdominal symptoms. Elevated CA-125 points toward an ovarian neoplasm, while CA 19-9 is commonly used to identify pancreatic cancer and monitor for disease progression. CA-125 levels greater than 75 U/ml were associated with decreased 5-year survival [8, 9].
The patients diagnosed with primary pancreatic adenocarcinoma that has metastasized to the ovaries usually present an ovarian mass prior to the pancreatic adenocarcinoma diagnostic [4].
In this patient, the clinical presentation was a generalized wasting syndrome, as well as an anemic syndrome due to severe anemia [10, 11]. CT findings show a complex unilateral ovarian mass and a dependent mass on the body and tail of the pancreas with a solid and cystic component. As the Krukenberg tumor was diagnosed, in the laparoscopy a left salpingo-oophorectomy was done. Since it is known that resecting the tumor increases the survival of patients; and reduces the risk of tumor infection, bleeding, or rupture during chemotherapy.
In this particular case the clinical presentation, as well as the unilateral presentation of the tumor, is not usual, and at final diagnosis with an immunohistochemistry pattern that marked CK7+ and CK 20-, also rare for a Krukenberg tumor. Also, we found a very rare mucosal metastasis to the lower gastrointestinal tract for ductal pancreatic cancer, the motive of another discussion.
Due to the fact that the patient had obstruction of the third portion of the duodenum, it was decided to perform a gastrojejunal bypass, since it represents a wide anastomosis, low levels of complications, and in expert hands, it can be done laparoscopically; in contrast to the endoscopic placement of a metal prosthesis, which is not so useful in complete obstructive lesions in the third portion of the duodenum, since it can migrate and are not exempt from complications and have a low success rate.
The main treatment for pancreatic cancer with ovarian metastases is surgery as soon as possible, with the goal of complete resection, even if the primary pancreatic cancer is unresectable. Resection of the ovarian metastasis is necessary, as it prolongs the survival time. Additionally, adjuvant chemotherapy with FOLFIRINOX (Drug combination: Fluorouracil, Irinotecan Hydrochloride, and Oxaliplatin) is advised as it constitutes front-line therapy for metastatic pancreatic ductal adenocarcinoma.
Following debulking surgery, our patient had initially received FOLFOX, to evaluate treatment response. 2 months later, the systemic chemotherapy with FOLFOX is still being continued and the patient is asymptomatic with a normal CA 19-9, free from Krukenberg tumor recurrence.
In clinical practice, pancreatic cancer presenting as KT is rare. They are easily misdiagnosed as primary ovarian carcinomas, especially if the ovarian involvement is unilateral, as in our case.
Consideration of KT in the differential will enable a timely diagnosis and optimal treatment, which includes complete resection of ovarian metastases.
Patients trend to a shorter median survival duration if they only were treated with chemotherapy alone without resection of the ovarian metastases than the patients who had undergone resection of ovarian metastases followed by chemotherapy [5]. All of these procedures were done as part of the supportive treatment to improve the quality of life of the patient and the median survival.
CONCLUSION
Resection of ovarian metastases combined with chemotherapy treatment may increase the survival duration even if the patient is in an advanced stage of the disease. Multidisciplinary management is required to avoid complications due to the progression of the disease and to support surgery as well as chemotherapy improves the survival of patients. Even though the Krukenberg tumor clinical presentation is bilateral adnexal mass, we can find it unilateral as a rare presentation. The common immunohistochemistry shows that the tumor regularly shows the expression of CK7 and CK20, the patient only showed CK7, meaning that there are other possibilities of presentation of the Krukenberg Tumor. Multidisciplinary interventions are required to make a final diagnosis of a Krukenberg tumor as it is easily misdiagnosed as a primary ovarian tumor.
ACKNOWLEDGMENT
Not applicable.
AUTHORS CONTRIBUTIONS
Samantha Sosa is the first author. SS and Alejandro Rossano wrote the manuscript. The study is designed by Alejandro Rossano. All authors read and approved the final manuscript.
FUNDING
No funding was received.
CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest.
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