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Home , Adenocarcinoma, Krukenberg tumor

Case report Friedrich Krukenberg of Krukenberg’s Tumor: Report of a series of cases

Martin Gómez Zuleta, MD,1 Luis Fernando Benito, MD,2 Cristina Almonacid, MD.3

1 Assistant Professor in the Gastroenterology Unit Abstract of the Department of Internal Medicine at the Universidad Nacional de Colombia and Hospital El Krukenberg’s tumor is an first described by the German physician Friedrich Krukenberg. It is a Tunal in Bogotá, Colombia of a primary tumor which is usually located in the stomach. This article presents a brief overview of 2 Third Year Surgery Resident at the Universidad de the history of these tumors and a series of 5 cases which were handled in our service. The aim of this article San Martin in Bogotá, Colombia 3 Pathologist at the Hospital El Tunal and the Clínica de is to demonstrate the complexity of this diagnosis, the therapeutic approach, and the pessimistic prognosis la Policía in Bogotá, Colombia that this condition has.

...... Received: 17-01-12 Key words Accepted: 15-05-12 Krukenberg’s tumor, gastric .

Friedrich Ernst Krukenberg (1871-1946) was a German of microscopic tubes and in Krukenberg tumors. In physician who worked in the city of Marburg under the 1981, Bouillon described in great detail what he called a tutelage of Felix Jacob Marchand, the Chief Medical Officer tubular (3-5). of the Department of , during his undergraduate The use of the term Krukenberg tumor is based on text- education (1846-1928). Dr. Marchand had had six cases of books published by Scully, Young and Kurman. It is defi- atypical ovarian tumors which he gave to Krukenberg as ned as a that occurs in the and which has material for his doctoral thesis. At the age of 25 years old in a significant component of stringy and typically 1896, Krukenberg published his thesis. He proposed that, has signet ring cells within a proliferative cellular stroma because of the appearance of malignant cells, these tumors derived from the normal stroma of the ovary. Small glands were a new type of primary ovarian which he with a squamous or large glands with intestinal named “fibrosarcoma ovarii mucocellulare (carcinomato- and mucinous epithelium can be found. In 2006 Kiyokawa, des) (1-3).” Young and Scully reported their experience with 120 cases In 1902 Schlagenhauffer proposed that these tumors of Krukenberg tumors. In the same year Lerwill and Young were not primary ovarian entities but rather were metasta- reported 4 cases of ovarian metastasis of gastric intestinal ses of epithelial neoplasia. Decades later it was confirmed type carcinoma (4-7). that Krukenberg tumor is in fact a metastasis of signet Nearly all Krukenberg tumors are considered to be ring cells typically from gastric which is metastases. However, there have been rare and isolated associated with disproportionate desmoplastic reactions. cases which have been interpreted as primary tumors. This explains the sizes reached by these lesions and the Krukenberg tumors constitute 1% to 1.5% of all ovarian prominent stromal component that puzzled Krukenberg tumors. Although they can occur at any age, most occur and Marchand. In 1928 Gauthier-Villars’ described a series between the ages of 30 and 40. They rarely occur during

© 2012 Asociaciones Colombianas de Gastroenterología, Endoscopia digestiva, Coloproctología y Hepatología 113 menopause. This tumor’s evolution and growth are rapid ding abdomen and . Bilateral ovarian masses found and are accompanied by significant degeneration. in the pelvic examination were confirmed by ultrasound Clinically, a patient presents gynecological symptoms and CT scan. Upper endoscopy showed a slight thicke- associated with ascites. The tumor is bilateral in up to 80% ning and convergence of folds in an area no bigger than of cases, and, because of its external structure and con- 1cm (Figure 5) near the greater curve of the upper third sistency, it does not present adhesions in the peritoneal of the stomach. taken from this location showed a cavity. Due to its histological composition it is classified as diffuse carcinoma. Endoscopic ultrasound showed ascites an epithelial tumor with connective tissue. It is transmitted and a hypoechoic lesion that destroyed all gastric layers in through contiguous tissue, blood, lymphatic cells through this area. The rest of the stomach was normal (Figure 6). the . Its mode of transmission has been the sub- The patient underwent bilateral salpingo-oophorectomy ject of ongoing study, and the exact pathway of its transmis- followed by but died 5 months later. sion has not yet been defined (10-12).

Clinical Cases

Case 1

A 48 year old woman came to the emergency department with abdominal pain and distension associated with 10kg weight loss and anorexia. A physical examination showed vital signs within normal limits and a patient who otherwise was not in the best condition. Patient presented major abdominal distention. An abdominal mass and ascites could be felt in the pelvic region, but there were no signs of peritoneal irritation. Patient was hospitalized for study. She tested positive for CA 125 (549), but normal for CA19.9 antigen (7.46). A complete abdominal ultrasound found positive evidence of a 16x3 cm mass in the right ovary and Figure 1. Dependent masses are observed in the , a 20 cm mass a 13x10 cm mass in the left ovary. An upper endoscopy in the right ovary and a 23 cm mass in the left ovary. showed an ulcerated lesion with infiltration extending from the upper third to the middle third of the corpus which was compatible with Borrmann III advanced gastric cancer. A CT scan showed a 20 cm mass in the right ovary and a 23cm mass in the left ovary (Figure 1). Her pathology revealed adenocarcinoma with diffuse ulcerated signet ring cells. After a week’s hospital stay for study, it was decided to initiate palliative treatment because of the prognosis of the patient. Surgery was performed by the gynecology service to resect the ovarian masses and reduce symptoms (Figure 2). Pathology showed signet ring cells not only within the ovarian stroma (Figure 3) but also within the fallopian tube (Figure 4). Patient’s postoperative evolution was adequate and was followed up with complementary chemotherapy. The patient died 4 months after diagnosis. Figure 2. Bilateral salpingo-oophorectomy, bilateral masses dependent Case 2 on left and right ovary are shown.

A 41 year old woman who complained of pelvic pain asso- Case 3 ciated with progressive alterations in her menstrual cycle and weight loss for 3 months was examined. Patient’s phy- A 48 year old woman with complaints of progressive pelvic sical condition was acceptable conditions. She was well pain and an abnormal menstrual cycle was examined. She hydrated, had pale mucous membranes, but had a protru- was found to be in poor condition with anemia, abdominal

114 Rev Col Gastroenterol / 27 (2) 2012 Case report Ovary replaced by a tumor with signet ring cells

Figure 3. Signet-ring cells infiltrating the ovary.

Figure 5. The arrow indicates an approximately 1 cm lesion, the only evidence of which is loss of folds at this level.

Uterine tube infiltrated by a tumor with signet ring cells

Figure 4. Signet-ring cells infiltrating the uterine tube. distension and a positive ascitic wave. Gynecologic eva- luation showed bilateral ovarian masses. Patient was hos- pitalized for testing. An abdominal CT scan showed bila- teral ovarian masses. Endoscopy showed an ulcerated and Figure 6. A focal lesion has destroyed all layers and thickened the infiltrative lesion compromising the entire gastric corpus gastric wall to 11.3 mm. Note the normal wall which measures 4.3 mm, which was diagnosed as Borrmann level IV cancer (Figure indicated by the arrow. 7). The pathology report showed a diffuse carcinoma. Due to the patient’s poor condition, she and her family chose not to undergo any treatment except for analgesia. She died branes, normal vital signs, ascites and bilateral ovarian mas- 2 months after diagnosis. ses. A pelvic CT scan showed bilateral ovarian masses. CA 125 tested at 712 (normal value: 33 IU/ml) and an endos- Case 4 copy showed an ulcerated lesion extending from the cardia to the angular incisure compromising the greater curve. A 50 year old woman with complaints of progressively It was reported as a Borrmann level III cancer. Pathology increasing abdominal girth, but with no other associated reported diffuse carcinoma. symptoms such as dyspepsia or gastrointestinal bleeding, The patient underwent surgery for removal of ovarian mas- was examined. Examination showed pink mucous mem- ses followed by chemotherapy. As in the previous three cases

Friedrich Krukenberg of Krukenberg’s Tumor: Report of a series of cases 115 gastric surgery was not performed. Development was accep- with the primary , but 20% to 30% occur following table, but the patient died 4 months following diagnosis. removal of the primary tumor. The prognosis of a patient with Krukenberg tumor is extremely poor with average sur- vival time between 3 and 10 months. Patients in our service survived 3.7 months on average. Only 10% of patients sur- vive more than two years after diagnosis (18-20).

Table 1. Main characteristics of the 5 patients evaluated with Krukenberg Tumors.

Case Age Endoscopy Pathology Treatment Evolution 1 48 Bormann III Diffuse Surgery and 4 months chemotherapy 2 41 Bormann III Diffuse Surgery and 5 months chemotherapy 3 48 Bormann IV Diffuse Pain 2 months medication 4 50 Bormann III Diffuse Palliation 4 months 5 32 Bormann II Diffuse Surgery and 4 months chemotherapy

Krukenberg tumors have two important characteristics. The first is ovarian metastasis characterized by the presence of signet ring cells, and second is pseudo prolifera- Figure 7. Ulcerated and infiltrative lesion that compromised the entire tion of ovarian stroma. By-products of neoplastic epithelial corpus and part of the antrum. cells induce proliferation of fused ovarian stromal cells and Case 5 abundant collagen deposits resulting in disproportionate desmoplastic reactions. It is important to note that these The patient was a 32 year old woman who was suffering tumors do not always have gastric origins: 76% originate from pelvic and perineal pain associated with progressive in the stomach, 11% in the bowel, 4% come from breast abdominal distension, vomiting, anorexia, but no weight cancer, 3% from the biliary system, 3% from the cecal loss. Symptoms had been developing for 2 months prior to and the remaining 3% come from the , consultation of evolution. Physical examination showed that cervix, bladder and renal pelvis. About 80% are bilateral. the patient was in generally poor condition with a distended When examined by pathology the ovaries have a smooth, abdomen and an ascitic wave. Patient was hospitalized for spongy or gelatinous consistency, although they can also be study by the gynecology department. A CT scan showed firm. This depends on the degree of edema, on aggregates bilateral ovarian masses with peritoneal tumor seeding. of mucin within the stroma, on the degree of hypercellula- Endoscopy showed an approximately 4 cm ulcerated lesion rity, and on the degree of fibrous transformation. The ovary with infiltration in the upper third of the posterior wall. It generally retains its shape despite the large size that these was diagnosed as Borrmann type II cancer. Pathology repor- lesions can reach. They range in size from 5 cm to larger ted a poorly differentiated ulcerated carcinoma with signet than 20 cm (as in the first case reported where the tumor in ring cells. The patient underwent surgery for resection of the left ovary reached 23 cm in diameter). gynecological ovarian masses. The tumor on the right ovary Immunological markers for this tumor include MUC 1, measured 20 cm x 20 cm while that on the left ovary mea- CK 7 and estrogen receptors which are of great importance. sured 15 cm x 10cm. Patient underwent chemotherapy with A good example of their importance is the second case we mixed results, but died 4 months after diagnosis. presented. The gastric tumor was very small (<2cm), but The table 1 shows the main characteristics of the five (5) the ovarian masses were very large and had ascites. Only patients evaluated with Krukenberg tumors. allowed us to confirm that the pri- mary tumor was in the stomach, and this completely chan- Discussion ged treatment and prognosis of the patient (22-24). Krukenberg tumor patients usually consult for abdomi- Krukenberg tumors account for 1% to 2% of all ovarian neo- nal and pelvic pain, changes in their menstrual cycles or plasms. In most cases this lesion is simultaneously diagnosed dyspareunia. In more advanced stages patients present asci-

116 Rev Col Gastroenterol / 27 (2) 2012 Case report tes. It is noteworthy that all 5 cases presented had ascites Conclusions indicating that these patients were in advanced stages. The second case is striking because the patient had a small gas- Krukenberg’s tumor should not be diagnosed in all patients tric lesion but already presented ascites and ovarian masses who have ovarian masses because there are many primary of 12 and 15cm. This gives us an idea of the aggressiveness tumors of this organ. Krukenberg’s tumor of the ovary is of these diffuse and raises the question of how a metastasis that has the histological patterns that we have these tumors spread. The pathways and mechanisms by discussed in this article. It is important to communicate which cancer cells reach the ovaries from the stomach, long with the medical team to identify the primary tumor before mystery, still remain only partially understood (10-12). surgery. Primary tumors are commonly located in the sto- Three possible pathways for metastasis have been con- mach but may be located in other organs including the sidered: lymphatic, hematic and peritoneal. Since these colon, rectum, , and pancreas. The prognoses for tumors show no peritoneal involvement on the ovarian patients with this type of metastatic tumor are poor: most surface and rarely involve the peritoneum, the theory of die within the first year of evolution. There are rare cases in peritoneal dissemination has been discarded. The lympha- which patients survive several years (26). tic route is most frequently postulated because lymphatic permeation resulting from carcinomatous emboli in adjoi- ReferencEs ning structures (ovarian hilum, mesovarium and meso- salpinx) is commonly found in the histological study of 1. Kim SH, Kim WH, Park KJ, Lee JK, Kim JS. CT and MR fin- these tumors. There are also many studies of patients with dings of Krukenberg tumors: comparison with primary ova- early gastric cancer and Krukenberg tumors which consi- rian tumors. J Comput Assist Tomogr 1996; 20(3): 393-8. der that the rich lymphatic plexuses that drain the gastric 2. Tavassoli FA, Devilee P (editors). WHO Classification mucosa and submucosa could be the route by which the Tumors of the Breast and Female Genital Organs. Lyon: tumor spreads to the ovary. It has been found that the risk IARC Press; 2003. 3. Irving JA, Lerwill MF, Young RH. Gastrointestinal stromal of ovarian compromise is greater when there are a larger tumors metastatic to the ovary: a report of five cases. Am J number of lymph nodes affected by gastric cancer (8, 9). Surg Pathol 2005; 29(7): 920-6. Some authors propose that the cancer spreads directly 4. Lash RH, Hart WR. Intestinal metastatic through the circulatory system via the thoracic lymph duct to the ovaries: a clinicopathologic evaluation of 22 cases. rather than through purely retrograde dissemination via Am J Surg Pathol 1987; 11(2): 114-21. the lymphatic route (22-24). 5. Mccluggage W, Wilkinson N. Metastatic invol- Since Krukenberg’s tumor is a metastatic tumor, it has ving the ovary: a review with an emphasis on morphological been proposed that the primary cancer must be found and and immunohistochemical features. 2005; treated first. Nevertheless, most cases have such poor prog- 47(3): 231-47. noses that radical surgery such as oophorectomies improve 6. Al-Agha OM, Nicastri AD. An in-depth look at Krukenberg survival only in cases of solitary ovarian metastases or local tumor: an overview. Arch Pathol Lab Med 2006; 130(11): extensions of the disease only located within the pelvis. 1725-30. 7. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, Chemotherapy and are indicated as adju- 2002. CA Cancer J Clin 2005; 55(2): 74-108. vant therapy for cytoreduction and gastric cancer control 8. Krukenberg F. Ueber das fibrosarcoma ovarii mucocellulare (car- which is no longer susceptible to surgical treatment. Even cinomatodes). Arch Gynaecol Obstet 1896; 50(2): 287-321. though we were already aware of the bad prognoses, in 4 9. Woodruff JD, Novak ER. The Krukenberg tumor: study of of the cases in this series bilateral salpingo-oophorectomies 48 cases from the ovarian tumor registry. Obstet Gynecol were performed. Since these tumors had apparently not 1960; 15: 351-60. disseminated elsewhere, we performed surgery primarily 10. Yakushiji M, Tazaki T, Nishimura H, Kato T. Krukenberg to reduce tumoral burdens before chemotherapy. Probably, tumors of the ovary: a clinicopathologic analysis of 112 to control Krukenberg’s tumor and avoid its bad prognosis cases. Acta Obstet Gynaecol Jpn 1987; 39(3): 479-85. we must prevent gastric carcinoma since, as is well known, 11. Hale RW. Krukenberg tumor of the ovaries. A review of 81 it has a strong genetic component identified as inheri- records. Obstet Gynecol 1968; 32(2): 221-5. 12. Israel SL, Helsel EV Jr, Hausman DH. The challenge of ted familial cancer associated with the CDH1 gene. If we metastatic ovarian carcinoma. Am J Obstet Gynecol 1965; identify a family that meets the Amsterdam criteria for 93(8): 1094-101. this tumor genetic testing should be performed to identify 13. Kakushima N, Kamoshida T, Hirai S, Hotta S, Hirayama T, mutations in the CDH-1 gene in asymptomatic relatives. If Yamada J, et al. Early gastric cancer with Krukenberg tumor a patient tests positive, he or she should have a gastrectomy and review of cases of intramucosal gastric cancers with to prevent the appearance of the tumor (23-25). Krukenberg tumor. J Gastroenterol 2003; 38(12): 1176-80.

Friedrich Krukenberg of Krukenberg’s Tumor: Report of a series of cases 117 14. Kim NK, Kim HK, Park BJ, Kim MS, Kim YI, Heo DS, et 21. Cheong JH, Hyung WJ, Chen J, Kim J, Choi SH, Noh SH. al. Risk factors for ovarian metastasis following curative Survival benefit of metastasectomy for Krukenberg tumors resection of gastric adenocarcinoma. Cancer 1999; 85(7): from gastric cancer. Gynecol Oncol 2004; 94(2): 477-82. 1490-9. 22. Taylor AE, Nicolson VM, Cunningham D. Ovarian metas- 15. de Palma P, Wronski M, Bifernino V, Bovani I. Krukenberg tases from primary gastrointestinal : the Royal tumor in pregnancy with virilization. A case report. Eur J Marsden Hospital experience and implications for adjuvant Gynaecol Oncol 1995; 16(1): 59-64. treatment. Br J Cancer 1995; 71(1): 92-6. 16. Cetin B, Aslan S, Akinci M, Atalay C, Cetin A. A long survi- 23. Mori T, Fujiwara Y, Yano M, Tamura S, Yasuda T, Takiguchi ving case of Pseudomeigs’ syndrome caused by Krukenberg S, et al. Prevention of peritoneal metastasis of human gastric tumor of the stomach. Jpn J Clin Oncol 2005; 35(4): 221-3. cancer cells in nude mice by S-1, a novel oral derivative of 17. Sugimoto Y, Endo K, Sakahara H, Nakajima K, Abe M, Torizuka 5-Fluorouracil. 2003; 64(2): 176-82. K, et al. Sequential measurement of serum CA 125 levels in 24. Gretschel S, Siegel R, Estévez-Schwarz L, Hünerbein M, Krukenberg’s tumor. Gan No Rinsho 1985; 31(15): 1893-7. Schneider U, Schlag PM. Surgical strategies for gastric can- 18. Kikkawa F, Shibata K, Ino K, Nomura S, Kajiyama H, Suzuki cer with synchronous peritoneal carcinomatosis. Br J Surg T, et al. Preoperative findings in non-gynecologic carcino- 2006; 93(12): 1530-5. mas metastasizing to the ovaries. Gynecol Obstet Invest 25. Yonemura Y, Bando E, Kawamura T, Ito H, Endo Y, Miura 2002; 54(4): 221-7. M, et al. Cytoreduction and intraperitoneal chemotherapy 19. Park SY, Kim HS, Hong EK, Kim WH. Expression of for carcinomatosis from gastric cancer. Cancer Treat Res 7 and 20 in primary of the stomach 2007; 134: 357-73. and colorectum and their value in the differential diagnosis 26. Xu DZ, Zhan YQ, Sun XW, Cao SM, Geng QR. Meta- of metastatic carcinomas to the ovary. Hum Pathol 2002; analysis of intraperitoneal chemotherapy for gastric cancer. 33(11): 1078-85. World J Gastroenterol 2004; 10(18): 2727-30. 20. Yook JH, Oh ST, Kim BS. Clinical prognostic factors for ovarian metastasis in women with gastric cancer. Hepatogastroenterology 2007; 54(75): 955-9.

118 Rev Col Gastroenterol / 27 (2) 2012 Case report