A case of virilization induced by a Krukenberg tumor from gastric cancer
© Hornung et al; licensee BioMed Central Ltd. 2008
Received: 15 August 2007
Accepted: 15 February 2008
Published: 15 February 2008
The Krukenberg tumor represents ovarian metastases associated with gastric cancer or other gastrointestinal malignancies. Histology shows typical mucus-production and numerous signet-ring cells. Occasionally Krukenberg tumors have endocrine function and, as a consequence, some patients demonstrate hirsutism and virilization.
Here we report a case of virilization associated with an extensive gastric adenocarcinoma and Krukenberg tumor in a premenopausal woman. Virilization occurred three months after diagnosis of gastric cancer and the ovarian tumors. Palliative chemotherapy was initiated as primary therapy, but gastric outlet obstruction required a gastrojejunostomy. In addition, oopherectomy was performed to relieve abdominal tension and to abate hormonal effects. It is likely that virilization of the patient could have been prevented by earlier oopherectomy prior to development of hormone production.
Despite the limitation in survival time early oopherectomy should be considered to prevent the development of virilization even in palliative situations if a Krukenberg tumor is diagnosed with gastric cancer.
Although incidence and mortality of gastric cancer have decreased over the last decades, it still remains the fourth most common cancer and the second leading cause of cancer-related death worldwide [1, 2]. In some cases secondary tumor from gastric signet-cell adenocarcinoma appear in the ovaries. It was first described by Krukenberg in 1896 . Histologically, Krukenberg tumors show diffuse stromal proliferation, mucus-production, and numerous signet-cells that usually can be found in both ovaries. In general, a mucus-producing gastric carcinoma with signet-cells in the stomach is diagnosed as a primary tumor. McGill et al. showed, that among 233 female patients with gastric cancer, there is an incidence of Krukenberg tumors of 18.2% in premenopausal women between 40 to 50 years-old, versus 0% in postmenopausal women . Diagnosis of Krukenberg tumors represents advanced malignancy and there is still no effective therapy for this type of tumor. Therefore, prognosis is poor and median survival of patients ranges between 7 to 14 months [4, 5].
Diagnosis is usually accomplished by CT scan or ultrasound . The literature reveals several reports of pregnant women suffering from Krukenberg tumor in association with virilization or hirsutism. In these cases, both mother and infant suffer from the clinical signs of elevated androgen levels [6, 7]. In this context one has to distinguish hirsutism, which describes an increase in body hair from virilization, with an additional change to male body features.
Here we report a case of a 41 years old female patient with Krukenberg tumor and strong signs of virilization without pregnancy. The case is of interest because it affected a non-pregnant patient and virilization occurred only three months after the initial diagnosis of Krukenberg tumor.
The Krukenberg tumor is an ovarian metastasis of a primary tumor derived from abdominal or retroperitoneal organs . Two-thirds of primary tumors are found in the stomach. The appendix, colon, small intestine, rectum, gallbladder and urinary bladder have also been reported as a site of the original carcinoma . Even intramucosal gastric cancer may lead to a Krukenberg tumor . Kiyokawa et al. reported in an extensive review of 120 cases that two-thirds of the Krukenberg tumors were diagnosed at the same time as the primary carcinoma . Our case parallels this experience, since diagnosis of the gastric tumor and the Krukenberg tumor were established by the same CT scan. On the other hand Schoenfeld et al. reported metachroneous occurrence of a Krukenberg tumor 8 years after subtotal gastrectomy for adenocarcinoma . In our case simultanous diagnosis was facilitated by clinical symptoms, which hinted to both organs. These signs were nausea, vomiting and upper abdominal tension in combination with hypermenorrhea, followed by amenorrhea. However, only abdominal swelling and abdominal pain are reported as symptoms of Krukenberg tumors, whereas abnormal vaginal bleeding and amenorrhea occur in only 20% of patients . Most patients with Krukenberg tumor are in the premenopausal period of life and at least two-thirds of the tumors are bilateral [4, 11]. Only a small number of patients have endocrine manifestations, including virilization, hirsutism, breast soreness and swelling, postmenopausal vaginal bleeding, as well as endometrial hyperplasia .
Published cases of Krukenberg tumor with virilization. None of them reported time delay between diagnosis of Krukenberg tumor and virilization.
Number of reported cases
Year of Publication
Interstitial hemorrhage and rupture of a Krukenberg tumor with virilism. Wagner et al. (21)
Krukenberg tumor complicating pregnancy; report of a case with androgenic activity. Fox et al. (6)
Virilization coexisting with Krukenberg tumor during pregnancy. Spadoni et al. (20)
Gonadotropin-dependent Krukenberg tumor causing virilization during pregnancy. Connor et al. (19)
Metabolism of testosterone by virilizing Krukenberg tumor of the ovary. Ances at al. (18)
A case of Krukenberg tumor with virilization aspects. Sani et al. (22)
Approach to the mechanism of androgen overproduction in a case of Krukenbery tumor responsible for virilization during pregnancy. Forest et al. (16)
Long-interval masculinizing Krukenberg tumor of the ovary. Schoenfeld et al. (12)
Clinical and ultrastructural findings of an androgenizing Krukenberg tumor in pregnancy. Silva et al. (15)
Tubular Krukenberg tumor in pregnancy with virilization. Fung et al. (14)
Krukenberg tumor in pregnancy with virilization. A case report. De Palma et al. (13)
Krukenberg tumor during pregnancy with maternal and fetal virilization: a difficult diagnosis. A case report. Vauthier-Brouzes et al. (7)
Krukenberg tumors of the ovary: a clinicopathologic analysis of 120 cases with emphasis on their variable pathologic manifestations. Kiyokawa et al. (11)
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Histologically the tumor consisted of mucus-producing glandular structures, small solid nests and numerous signet-ring cells surrounded by partly luteinized ovarian stroma. In immunohistochemical studies the tumor cells showed a strong expression of cytokeratin 7 and focal expression of cytokeratin 20 consistent with the diagnosis of gastric adenocarcinoma. The neuroendocrine markers CD56, chromogranin and synaptophysin were negative ruling out a neuroendocrine subpopulation of the tumor. In addition, Krukenberg tumors of patients with virilization reveal a stromal luteinization, whereas these microscopic findings can be confirmed in only 1 of 4 patients with hirsutism. Furthermore only 6 of 97 patients lacking stromal luteinization have been shown to have endocrine changes. Therefore, it appears that androgenizing hormone production requires development of luteinized stroma in Krukenberg tumors and it is likely that early ovarectomy can prevent virilization since spontaneous regression of virilization is a rare event .
In the present case, virilization appeared only three months after the diagnosis of Krukenberg tumor. The case suggests that hormone production leading to virilization requires a minimum period of three months. We therefore propose that a timely control of androgenizing hormones should be performed in cases of Krukenberg tumor derived from gastric cancer. Due to the possibility of rapidly developing virilization, surgical resection of symptomatic and hormone producing tumors should be offered to patients even in a palliative setting.
Written content was obtained from the patient for publication of this report.
Prof. Dr. Edward Geissler, Regensburg, is acknowledged for helpful suggestions drafting the manuscript.
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