Arch Pathol Lab Med—Vol 130, November 2006 An In-depth Look at Krukenberg Tumor—Al-Agha & Nicastri 1725

An In-depth Look at Krukenberg TumorAn Overview

Osama M. Al-Agha, MD; Anthony D. Nicastri, MD

● Krukenberg tumor is an uncommon metastatic tumor ofthe ovary. This article provides an overview of the majorpathologic manifestations of Krukenberg tumor, patientcharacteristics, clinical and laboratory features of the dis-ease, prognostic factors, and current knowledge about itspathogenesis. Pathologists have to be familiar with the di-agnostic histopathologic features of the tumor and its prin-cipal differential diagnoses. Awareness of the diagnosticmanifestations of the tumor leads to the correct diagnosisand prevents tumor misclassification, thus avoiding im-proper clinical management. The article also addresses thepotential clinical utility of serum CA 125 in patients withKrukenberg tumors. Prognosis of Krukenberg tumor is stillvery poor but our review of the literature reveals severalfactors that appear to have an impact on survival. There isno established treatment for Krukenberg tumors. A nation-al registry and prospective studies are needed to set a ther-apeutic approach for Krukenberg tumors in the hope ofimproving the survival rate.

(Arch Pathol Lab Med. 2006;130:1725–1730)

Krukenberg tumor is a metastatic signet ring cell ade-nocarcinoma of the ovary. Krukenberg tumor is un-

common, accounting for 1% to 2% of all ovarian tumors.In 1896, Friedrich Krukenberg (1871–1946), a German gy-necologist and pathologist, described what he presumedwas a new type of primary ovarian neoplasm. The truemetastatic nature of this lesion was established 6 yearslater. Stomach is the primary site in most Krukenberg tu-mor cases (70%). Carcinomas of colon, appendix, andbreast (mainly invasive lobular carcinoma) are the nextmost common primary sites. Rare cases of Krukenbergtumor originating from carcinomas of the gallbladder, bil-iary tract, pancreas, small intestine, ampulla of Vater, cer-vix, and urinary bladder/urachus have been reported.1

The interval between the diagnosis of a primary carcino-ma and the subsequent discovery of ovarian involvementis usually 6 months or less, but longer periods have beenreported. In many cases, the primary tumor is very small

Accepted for publication May 12, 2006.From the Department of Pathology, State University of New York,

Brooklyn.The authors have no relevant financial interest in the products or

companies described in this article.Reprints: Osama M. Al-Agha, MD, Department of Pathology, State

University of New York Downstate Medical Center, 450 Clarkson Ave,Box 25, Brooklyn, NY 11203 (e-mail: osama.al-agha@downstate.eduor osamaalagha@yahoo.com).

and can escape detection. A history of a prior carcinomaof the stomach or another organ can be obtained in only20% to 30% of the cases.2

It is well recognized that adenocarcinomas composed ofsignet ring cells of various organs tend to metastasize tothe ovaries much more commonly than adenocarcinomasof other histologic types from the same sites. Of these,gastric adenocarcinoma of signet ring cell type (alsoknown as infiltrative or diffuse gastric adenocarcinoma),chiefly from the pylorus, is the most common finding.3,4

The frequency of Krukenberg tumor varies with that ofgastric carcinoma in the population analyzed. For exam-ple, in countries such as Japan, which has a high preva-lence of gastric carcinoma, Krukenberg tumor accounts fora large proportion (17.8%) of all ovarian cancers.5

ROUTE OF METASTASISKrukenberg tumor is an example of the selective spread

of cancers, most commonly in the stomach-ovarian axis.This axis of tumor spread has historically drawn the at-tention of many pathologists, especially when it was foundthat gastric neoplasms selectively metastasize to the ova-ries without involvement of other tissues.6 The route ofmetastasis of gastric carcinoma to the ovaries has been amystery for a long time, but it is now evident that retro-grade lymphatic spread is the most likely route of metas-tasis as there are several evidences supporting this con-cept. First, lymphatic permeation at the hilum and cortexis microscopically noted in many cases of Krukenberg tu-mor. Second, review of the literature reveals 8 reportedcases of Krukenberg tumors with primary gastric carci-nomas that were confined to the mucosa and submucosa.7It should be remembered that gastric mucosa and sub-mucosa have a rich lymphatic plexus and their invasionusually accounts for the spread of early gastric cancers.Thus, development of Krukenberg tumors in these casesof early gastric cancers can be explained on the basis oflymphatic spread. Third, some studies showed that therisk of ovarian metastasis in gastric carcinoma increaseswhen there is an increased number of metastatic lymphnodes.8 Last, peritoneal involvement is usually absent andthe external surface of the ovaries in Krukenberg tumorsoften lacks any seedings, adhesions, implantations, or tu-mor infiltrations—an observation that may oppose theperitoneal spread theory and further supports the theoryof retrograde lymphatic spread.

DOES PRIMARY KRUKENBERG TUMOR EXIST?The primary carcinoma in Krukenberg tumors is some-

times clinically occult. Careful thorough examination of

1726 Arch Pathol Lab Med—Vol 130, November 2006 An In-depth Look at Krukenberg Tumor—Al-Agha & Nicastri

Figure 1. Abdominopelvic computed tomographic scan of a 67-year-old woman with a Krukenberg tumor originating from a primary gastriccarcinoma. The tumor appears radiologically as bilateral, solid ovarianmasses.

the gastrointestinal tract and other sites may also fail toreveal the primary carcinoma. The primary carcinomasometimes may remain undetected for several years afteroophorectomy. Therefore, a diagnosis of ‘‘primary Kru-kenberg tumor’’ has been proposed for some cases inwhich either there is long-term survival after Krukenbergtumor resection without detection of the primary tumor,or a complete autopsy examination fails to reveal an extra-ovarian primary tumor.9 However, many authors are re-luctant to accept the term primary Krukenberg tumor for thefollowing reasons. (1) Primary carcinomas, particularlythose arising in the breast and stomach, may be verysmall, requiring exhaustive sectioning to detect them, andit is possible that tiny primary tumors were missed in thereported cases of primary Krukenberg tumors; (2) it isknown that mammary and gastric carcinomas may remainsilent for many years. The clinical occultness of the pri-mary tumors probably accounts for some reported pri-mary Krukenberg tumors, especially if one knows that thesurvival rate of patients with Krukenberg tumor is low(less than 2 years on average) and most of the patients donot live long enough for the primary to become clinicallydetectable; (3) some primary ovarian tumors may havesignet ring cells, and this may be responsible for somereported cases of primary Krukenberg tumor in the earlierliterature. These tumors include the primary ovarian, mu-cinous carcinoid, and the signet ring stromal tumor of theovary, as will be discussed later. Overall, we believe that,although primary Krukenberg tumor may exist, oneshould exercise considerable caution before making sucha diagnosis or accepting reported cases of primary Kru-kenberg tumors as valid.

CLINICAL PROFILESWomen with Krukenberg tumors tend to be unusually

young for patients with metastatic carcinoma as they aretypically in the fifth decade of their lives, with an averageage of 45 years. This young age of distribution can berelated in part to the increased frequency of gastric signetring cell carcinomas in young women.10 Common pre-senting symptoms are usually related to ovarian involve-ment, the most common of which are abdominal pain anddistension (mainly because of the usually bilateral and of-ten large ovarian masses). The remaining patients havenonspecific gastrointestinal symptoms or are asymptom-atic. In addition, Krukenberg tumor is reportedly associ-ated with virilization resulting from hormone productionby ovarian stroma.11 Ascites is present in 50% of the casesand usually reveals malignant cells. Cetin et al12 have re-cently reported a case of Krukenberg tumor with righthydrothorax and ascites that revealed no malignant cells.This was referred to as pseudo-Meig syndrome (in contrastto Meig syndrome, which is the triad of benign ovariantumor, ascites, and right hydrothorax). The diagnosis ofthe primary carcinoma can be made either preoperatively,during the operation for the ovarian metastasis, or withina few months postoperatively.1 Often, the primary tumoris too small to be detected. In such a situation, diagnosisof Krukenberg tumor warrants careful radiographic andendoscopic exploration of the digestive system in an at-tempt to detect the primary carcinoma. Radiologically,Krukenberg tumors on abdominopelvic sonography andcomputed tomographic scans usually appear as bilateralovarian masses. The masses are usually solid but can alsobe cystic13 (Figure 1, arrows).

PATHOLOGIC FEATURESGross Features

Krukenberg tumors are bilateral in more than 80% ofthe reported cases. The ovaries are usually asymmetricallyenlarged, with a bosselated contour. The sectioned surfac-es are yellow or white; they are usually solid, althoughthey are occasionally cystic (Figure 2). Importantly, thecapsular surface of the ovaries with Krukenberg tumorsis typically smooth and free of adhesions or peritonealdeposits. Of note, other metastatic tumors to the ovarytend to be associated with surface implants. This may ex-plain why the gross morphology of Krukenberg tumor candeceptively appear as a primary ovarian tumor. However,bilateralism in Krukenberg tumor is consistent with itsmetastatic nature.

Microscopic Features

Microscopically, Krukenberg tumor has 2 components:epithelial and stromal. The epithelial component is com-posed chiefly of mucin-laden signet ring cells with eccen-tric hyperchromatic nuclei. The cytoplasm of the signetring cells can be eosinophilic and granular (Figure 3, A),pale and vacuolated (Figure 3, B), or it can have a bull’seye (targetoid) appearance containing a large vacuole witha central to paracentral eosinophilic body composed of adroplet of mucin (Figure 4, arrows). Some tumor cells maylack a mucin vacuole. Mitotic activity is sparse. The signetring cells can be single, clustered, nested, or they can bearranged in tubules, acini, trabeculae, or cords. Severaldifferent patterns can appear in one tumor. Krukenbergtumors displaying a predominantly tubular pattern havebeen subclassified as tubular Krukenberg to distinguishthem from the classic type (Figure 5). In tubular Kruken-berg tumors, the signet ring cells are present in tubulesand intermingled with stromal cells.14 The histochemical

Arch Pathol Lab Med—Vol 130, November 2006 An In-depth Look at Krukenberg Tumor—Al-Agha & Nicastri 1727

Figure 2. Krukenberg tumor of the same patient as in Figure 1. Theovaries are asymmetrically enlarged with a bosselated contour. Crosssection of the ovaries shows predominantly yellow, solid tumor tissue.

Figure 3. Krukenberg tumor showing numerous signet ring cells pre-sent within a cellular stroma. The cytoplasm of the signet ring cells canbe eosinophilic and granular (A) or pale and vacuolated (B) (hematox-ylin-eosin, original magnifications �600).

identification of intracytoplasmic mucin in the signet ringcells is essential for Krukenberg tumor diagnosis.15 Be-cause the intracytoplasmic mucins of the signet ring cellsare neutral and acidic (mostly sialomucins), they stainwith Mayer mucicarmine (Figure 6, A), periodic acid–Schiff with diastase digestion, and Alcian blue stains. Im-munohistochemically, the tumor cells are immunoreactiveto epithelial markers, such as cytokeratins (AE1/AE3)(Figure 6, B), and epithelial membrane antigen, and they

do not show immunoreactivity to vimentin and inhibin.16

The mesenchymal component of Krukenberg tumor is ofovarian stromal origin and is composed of plump andspindle-shaped cells with minimal cytologic atypia or mi-totic activity. Stromal edema can be present focally but issometimes diffuse and marked to the extent of formingpseudocysts. Sometimes the desmoplastic reaction in thestroma can be so intense that it obscures the signet ringpattern of the tumor, rendering its diagnosis challenging,and possibly confused with fibromas (Figure 7). Mucin-special stains can highlight the signet ring cells, facilitat-ing the correct diagnosis.1–4

CA 125 IN KRUKENBERG TUMORPreoperative serum CA 125 levels in patients with Kru-

kenberg tumors can be elevated, though they subsequentlydecrease after tumor resection.17 On the basis of this ob-servation, serum CA 125 level can be used for (1) post-operative follow-up of patients for evaluation of completeresection of the tumor, and (2) follow-up of patients witha history of primary adenocarcinomas (gastrointestinal, inparticular) for early detection of ovarian metastasis. SerumCA 125 level also can help predict the prognosis. In astudy that investigated serum CA 125 levels in Kruken-berg tumors, it was found that the 5-year survival rate waslower in patients in whom preoperative serum CA 125 lev-els were greater than 75 U/mL compared with patientswith CA 125 levels less than 75 U/mL.18

DIFFERENTIAL DIAGNOSISThe diagnosis of Krukenberg tumors largely depends

on the recognition of its characteristic light microscopicfeatures with hematoxylin-eosin–stained sections. How-ever, Krukenberg tumors may mimic other metastatic orprimary ovarian tumors. Distinction from the latter is ofgreat importance as misclassification of Krukenberg tumoras a primary ovarian tumor may lead to suboptimal treat-ment of the patient. To facilitate discussion of differentialdiagnosis of Krukenberg tumor, the diagnosis is dividedinto 2 major parts according to the histologic subtype ofKrukenberg tumor. The distinction should be made be-tween (1) classic Krukenberg tumor and ovarian tumorswith signet ring cells, and (2) tubular Krukenberg tumorsand ovarian tumors with tubular pattern.

Differential Diagnosis of Classic Krukenberg TumorClassic Krukenberg tumors (ie, tumors in which the sig-

net ring cells lack tubular formation) must be distin-guished from ovarian tumors that contain signet ring cellsfilled with either mucinous or nonmucinous material.

Ovarian Tumors With Signet Ring Cells ContainingMucin. This group contains primary mucinous carcino-ma and mucinous carcinoid tumors. Primary mucinous tu-mors of the ovary can contain cells with signet ring ap-pearance at least focally. However, these tumors tend tobe more commonly unilateral with a complex papillarypattern.19 Mucinous carcinoid tumors (either primary ormetastatic, most commonly from appendix) enter the dif-ferential diagnosis in this group by having cells that mayassume signet ring appearance and resemble Krukenbergtumor cells. Although mucinous carcinoid cells stain withmucin stains similar to Krukenberg tumor cells, immu-nostains for chromogranin and synaptophysin are usuallypositive and can easily confirm the diagnosis in favor ofmucinous carcinoid.1–7

1728 Arch Pathol Lab Med—Vol 130, November 2006 An In-depth Look at Krukenberg Tumor—Al-Agha & Nicastri

Figure 4. Krukenberg tumor showing some signet ring cells with a bull’s eye or targetoid appearance containing a large vacuole with a centralor paracentral droplet of mucin that appears as an eosinophilic body (arrows) (hematoxylin-eosin, original magnification �600).

Figure 5. Krukenberg tumor cells can be arranged in tubules and cords (arrow). The tubules are lined with round-to-oval nuclei with high-gradecytologic atypia (hematoxylin-eosin, original magnification �400).

Figure 6. A, Krukenberg tumor with signet ring cells highlighted with mucicarmine. B, The signet ring cells of Krukenberg tumor are immuno-reactive with antibodies against cytokeratins (original magnifications �400).

Figure 7. At this power of magnification, the appearance of this area of Krukenberg tumor is similar to that of an ovarian fibroma, but occasionalsignet ring cells are evident on careful inspection (arrows) (hematoxylin-eosin, original magnification �200).

Ovarian Tumors With Signet Ring Cells ContainingNonmucinous Material. Krukenberg tumors must alsobe distinguished from ovarian tumors that can containsignet ring cells filled with nonmucinous material, includ-ing signet ring stromal tumor, sclerosing stromal cell tu-mor, and clear cell adenocarcinoma of the ovary. In con-

trast to Krukenberg tumor, signet ring stromal tumors arebenign, unilateral, devoid of epithelial differentiation, andtherefore positive for vimentin but negative for cytokera-tins.20 Sclerosing stromal cell tumor can have vacuolatedcells with signet ring appearance resembling Krukenbergtumor cells, but sclerosing stromal cell tumor cells contain

Arch Pathol Lab Med—Vol 130, November 2006 An In-depth Look at Krukenberg Tumor—Al-Agha & Nicastri 1729

lipid as opposed to mucin, which is found in Krukenbergcells, and therefore do not show reactivity to the periodicacid–Schiff stain. Moreover, Krukenberg tumor lacks thedistinctive microscopic features of sclerosing stromal celltumor (biphasic pattern composed of highly vascular andcellular areas separated by paucicellular areas). In addi-tion, a positive inhibin stain can help with the diagnosisof sclerosing stromal cell tumor. Clear cell carcinoma ofthe ovary may have cells with signet ring cell appearance,thus resembling classic Krukenberg tumors, at least focal-ly. In contrast to mucin-laden signet ring cells of Kruken-berg tumor, the clear cell cytoplasm contains glycogen, afeature that can be demonstrated with a periodic acid–Schiff stain, whose reactivity abolishes with diastase di-gestion. Besides, the papillary and tubulocystic patternwith hobnail cells characterize the clear cell carcinoma.

Differential Diagnosis of Tubular Krukenberg TumorTubular Krukenberg tumors (ie, tumors in which the

cells are predominantly arranged in tubules) must be dis-tinguished from other ovarian tumors displaying annularor tubular pattern. The major tumor in this group is Ser-toli-Leydig cell tumor. The nuclei of tubular Krukenbergtumors are more atypical than those within the tubules ofSertoli-Leydig cell tumors. Presence of signet ring cellswithin the tubules is inconsistent with Sertoli-Leydig celltumor. In contrast to Krukenberg tumor, Sertoli-Leydigcell tumor stains positive to inhibin but negative to cyto-keratins or epithelial membrane antigen. Other ovarian tu-mors with a tubular pattern that can enter the differentialdiagnosis in this group include well-differentiated endom-etrioid carcinoma (metastatic or primary) and tumors ofwolffian origin. Differentiation can be made on the basisof their characteristic histologic features.

IMMUNOHISTOCHEMISTRY IN THE DISTINCTION OFMETASTATIC CARCINOMAS FROM PRIMARY

OVARIAN NEOPLASMSImmunohistochemical evaluation may aid in distin-

guishing primary ovarian carcinomas from metastatic car-cinomas. Cytokeratins 7 and 20 (CK7 and CK20) immu-nophenotype is the most commonly used analysis. Pri-mary ovarian carcinomas are almost always immunore-active to CK7 (90%–100%) but generally are notimmunoreactive to CK20. By contrast, metastatic gastriccarcinoma tends to be less frequently positive for CK7(55%) but is positive for CK20 in approximately 70% ofcases. Colorectal adenocarcinomas are usually negative forCK7 but positive for CK20 in most cases. Tumors metas-tasizing from the appendix are commonly positive forCK20 but positive also for CK7 in 50% of cases. Therefore,a CK7�/CK20� immunophenotype favors a primary ovar-ian carcinoma, whereas a CK7�/CK20� or CK7�/CK20�

immunophenotype (CK20 positivity, in particular) favorsa metastatic gastrointestinal carcinoma.21–23

Use of source-specific antibodies can increase the di-agnostic confidence. For example, immunoreactivity forcarcinoembryonic antigen and CDX2 together with theimmunoexpression pattern of CK7�/CK20� increases theconfidence in pointing toward the colorectal origin of theprimary.24

PROGNOSIS AND MANAGEMENTPatients with Krukenberg tumors have an overall mor-

tality rate that is significantly high. Authors in almost all

the reported cases underline the gloomy outcome of thistumor. Most patients die within 2 years (median survival,14 months).25 Review of the literature showed that theprognostic factors for Krukenberg tumors have not beenwell established, but we were able to identify a numberof diagnostic and management issues that appear to havean impact on survival. Several studies show that the prog-nosis is poor when the primary tumor is identified afterthe metastasis to the ovary is discovered, and the prog-nosis becomes worse if the primary tumor remains covert.This has been supported by a study that showed that thesurvival rate was low in the patients who underwent sur-gery on the ovarian tumor simultaneously or before thesurgery on the primary carcinoma, compared with thesurvival rate of patients who underwent surgery on theovarian tumor after the surgery on the primary carcino-ma.18 Our review of the literature did not show large dif-ferences in the survival rate in regard to origin of the can-cer, except for 1 study that showed that the median sur-vival time of patients with ovarian metastases of gastriccarcinoma was lower than that of patients with breast andcolorectal carcinoma.26

No optimal treatment strategy for Krukenberg tumorshas been clearly established in the literature. Whether asurgical resection should be performed has not been ad-equately addressed. Lower rate of resectability when theprimary tumor metastasizes to other sites (in addition tothe ovaries) and the overall dismal prognosis are the 2major factors that usually dissuade resection of Kruken-berg tumors.27 On the contrary, if metastasis is limited tothe ovaries, surgery may render the patient free of residualdisease and the survival time may increase.28 Hence, thesignificance of early detection of ovarian metastasis andthe importance of serum CA 125 level monitoring (as dis-cussed previously) are vital. Chemotherapy or radiother-apy has no significant effect on prognosis of patients withKrukenberg tumors.

Because no curative treatment is available, prophylaxisby bilateral oophorectomy at time of operation of the pri-mary tumor has been considered by some authorities,29

but this requires further study and evaluation.

CONCLUSIONS

Krukenberg tumor is a metastatic ovarian tumor that ishistologically characterized by mucin-laden signet ringcells. Stomach is the most common primary site, but otherorgans can serve as a primary site. The lymphatic systemis the most likely route for metastasis. Diagnosis of Kru-kenberg tumor with unknown primary warrants carefulinvestigation of mainly the digestive tract and other po-tential sites. CA 125 levels can be used for screening forearly detection of ovarian metastasis as well as for moni-toring the course of disease. The prognosis of Krukenbergtumor is poor and no curative treatment is currently avail-able.

References1. Hale RW. Krukenberg tumor of the ovaries: a review of 81 records. Obstet

Gynecol. 1968;32:221–225.2. Holtz F, Hart WR. Krukenberg tumors of the ovary: a clinicopathological

analysis of 27 cases. Cancer. 1982;50:2438–2447.3. Duarte I, Llanos O. Patterns of metastases in intestinal and diffuse types of

carcinoma of the stomach. Hum Pathol. 1981;12:237–242.4. Rosai J. Rosai and Ackerman’s Surgical Pathology. Vol 2. 9th ed. St Louis,

Mo: The CV Mosby Co; 2004:1708.5. Yakusshiji M, Tazaki T, Nishimura H, Kato T. Krukenberg tumors of the ovary:

a clinicopathological analysis of 112 cases. Acta Obstet Gynaecol Jpn. 1987;39:479–485.

1730 Arch Pathol Lab Med—Vol 130, November 2006 An In-depth Look at Krukenberg Tumor—Al-Agha & Nicastri

6. Willis RA. The Spread of Tumours in the Human Body. 3rd ed. London,England: Butterworths; 1973:222–226.

7. Kakushima N, Kamoshida T, Hirai S, et al. Early gastric cancer with Kru-kenberg tumor and review of cases of intramucosal gastric cancers with Kruken-berg tumor. J Gastroenterol. 2003;38:1176–1180.

8. Kim NK, Kim HK, Park BJ, et al. Risk factors for ovarian metastasis followingcurative resection of gastric adenocarcinoma. Cancer. 1999;85:1490–1499.

9. Scully RE, Young RH, Clement PB. Tumors of the Ovary, Maldeveloped Go-nads, Fallopian Tube, and Broad Ligament. Washington, DC: Armed Forces Instituteof Pathology; 1999:81–105. Atlas of Tumor Pathology; 3rd series, fascicle 23.

10. Tso PL, Bringaze WL III, Dauterive AH, Correa P, Cohn I Jr. Gastric car-cinoma in the young. Cancer. 1987;59:1362–1365.

11. de Palma P, Wronski M, Bifernino V, Bovani I. Krukenberg tumor in preg-nancy with virilization: a case report. Eur J Gynaecol Oncol. 1995;16:59–64.

12. Cetin B, Aslan S, Akinci M, Atalay C, Cetin A. A long surviving case ofPseudomeigs’ syndrome caused by Krukenberg tumor of the stomach. Jpn J ClinOncol. 2005;35:221–223.

13. Kim SH, Kim WH, Park KJ, Lee JK, Kim JS. CT and MR findings of Kru-kenberg tumors: comparison with primary ovarian tumors. J Comput Assist Tom-ogr. 1996;20:393–398.

14. Fung MF, Vadas G, Lotocki R, Heywood M, Krepart G. Tubular Krukenbergtumor in pregnancy with virilization. Gynecol Oncol. 1991;41:81–84.

15. Ramzy I. Signet ring stromal tumor of ovary: histochemical, light, and elec-tron microscopic study. Cancer. 1976;38:166–172.

16. Wong PC, Ferenczy A, Fan L-D, McCaughey E. Krukenberg tumors of theovary: ultrastructural, histochemical, and immunohistochemical studies of 15 cas-es. Cancer. 1986;57:751–760.

17. Sugimoto Y, Endo K, Sakahara H, et al. Sequential measurement of serumCA 125 levels in Krukenberg’s tumor [in Japanese]. Gan No Rinsho. 1985;31:1893–1897.

18. Kikkawa F, Shibata K, Ino K, et al. Preoperative findings in nongynecologic

carcinomas metastasizing to the ovaries. Gynecol Obstet Invest. 2002;54:221–227.

19. Lee KR, Young RH. The distinction between primary and metastatic mu-cinous carcinomas of the ovary: gross and histologic findings in 50 cases. Am JSurg Pathol. 2003;27:281–292.

20. Vang R, Bague S, Tavassoli FA, Prat J. Signet ring stromal tumor of theovary: clinicopathologic analysis and comparison with Krukenberg tumor. Int JGynecol Pathol. 2004;23:45–51.

21. Park SY, Kim HS, Hong EK, Kim WH. Expression of cytokeratins 7 and 20in primary carcinomas of the stomach and colorectum and their value in thedifferential diagnosis of metastatic carcinomas to the ovary. Hum Pathol. 2002;33:1078–1085.

22. Wauters CC, Smedts F, Gerrits LG, Bosman FT, Ramaekers FC. Keratins 7and 20 as diagnostic markers of carcinomas metastatic to the ovary. Hum Pathol.1995;26:852–855.

23. Ronnett BM, Kurman RJ, Shmookler BM, Sugarbaker PH, Young RH. Themorphologic spectrum of ovarian metastases of appendiceal adenocarcinomas: aclinicopathologic and immunohistochemical analysis of tumors often misinter-preted as primary ovarian tumors or metastatic tumors from other gastrointestinalsites. Am J Surg Pathol. 1997;21:1144–1155.

24. Baker PM, Oliva E. Immunohistochemistry as a tool in the differential di-agnosis of ovarian tumors: an update. Int J Gynecol Pathol. 2005;24:39–55.

25. Benaaboud I, Ghazli M, Kerroumi M, Mansouri A. Krukenberg tumor: 9cases report [in French]. J Gynecol Obstet Biol Reprod (Paris). 2002;31:365–370.

26. Demopoulos RI, Touger L, Dubin N. Secondary ovarian carcinoma: a clin-ical and pathological evaluation. Int J Gynecol Pathol. 1987;6:166–175.

27. Novak E, Gray LA. Krukenberg tumors of the ovary: clinical and patho-logical study of 21 cases. Surg Gynecol Obstet. 1938;66:157–167.

28. Kim HK, Heo DS, Bang YJ, Kim NK. Prognostic factors of Krukenberg’stumor. Gynecol Oncol. 2001;82:105–109.

29. McGill FM, Ritter DB, Rickard CS, Kaleya RN. Krukenberg tumors: canmanagement be improved? Gynecol Obstet Invest. 1999;48:61–65.