Krukenberg tumor

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Krukenberg tumor
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Krukenberg tumor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Soujanya Thummathati, MBBS [2]

Synonyms and Keywords: Carcinoma mucocellulare; Ovarian tumor

Overview

Krukenberg tumor is a rare metastatic signet ring cell adenocarcinoma of the ovary.[1] Krukenberg tumor was first described as a new type of primary ovarian malignancy by Friedrich Ernst Krukenberg (1871–1946), a German gynecologist and pathologist, in 1896 which was later confirmed to be of metastatic gastrointestinal tract origin.[1] The pathogenesis of Krukenberg tumors involves metastasis of tumor cells from the stomach, appendix or colon to the ovaries.[2] Metastasis is more likely via the lymphatic spread. However, direct seeding across the abdominal cavity may also occur. On gross pathology, asymmetrically enlarged ovaries with a bosselated contour, usually solid, yellow or white cross sectioned surfaces, and the absence of adhesions or peritoneal deposits are characteristic findings of Krukenberg tumors.[1] Krukenberg tumor must be differentiated from primary mucinous carcinoma, mucinous carcinoid tumor, signet ring stromal tumor, sclerosing stromal cell tumor, clear cell adenocarcinoma of the ovary, and sertoli-leydig cell tumor.[1] The incidence of Krukenberg tumors is estimated to be approximately 0.16 per 100,000 individuals.[3][4] Krukenberg tumor is more commonly observed among women in their fifth decade of lives, with an average around 45 years of age. The majority of patients with Krukenberg tumor remain asymptomatic or have non-specific gastrointestinal symptoms.[1] Early clinical features include abdominal pain and distension(from the large, bilateral ovarian masses). If left untreated, patients with Krukenberg tumors may progress to develop virilization from the excessive hormone production from the ovarian stroma.[5] Prognosis is generally poor, and the 5 ­year survival rate of patients with Krukenberg tumor is lower in patients in with a preoperative serum CA-125 levels greater than 75 U/mL when compared with patients with CA-125 levels less than 75 U/mL.[6] The median survival of patients is between 7 to 14 months.[5] X rays, ultrasound, CT, MRI and immunohistochemistry help in the diagnosis of Krukenberg tumors. Management of Krukenberg tumors is driven by the identification and treatment of the primary cancer. Bilateral oophorectomy may only be performed for patients where the metastasis is localized to the ovaries.[7] The significance of early detection of ovarian metastasis and the importance of monitoring serum CA-125 level may improve the prognosis. Surgical resection may not be an option if the tumor has already metastasized to other sites.

Historical Perspective

Krukenberg tumor was first described as a new type of primary ovarian malignancy by Friedrich Ernst Krukenberg (1871–1946), a German gynecologist and pathologist, in 1896 which was later confirmed to be of metastatic gastrointestinal tract origin.[1]

Pathophysiology

  • The majority of Krukenberg tumors are bilateral.[1]
  • Stomach and colon are the primary sites in the majority of Krukenberg tumor cases (70%).[1]
  • The pathogenesis of Krukenberg tumors involves metastasis of tumor cells from the stomach, appendix, or colon to the ovaries.[2]
  • On gross pathology, asymmetrically enlarged ovaries with a bosselated contour, usually solid, yellow or white cross sectioned surfaces, and the absence of adhesions or peritoneal deposits are characteristic findings of Krukenberg tumors.[1]
  • On microscopic histopathological analysis, Krukenberg tumors are characterized by the following features:
    • Tumor composed of two components:
      • Epithelial
      • Stromal
        • Plump and spindle-shaped cells with minimal cytologic atypia or mitotic activity
        • Focal or diffuse stromal edema which may form pseudo cysts
        • Desmoplastic reaction may be present
  • Stomach is the primary site in the majority of Krukenberg tumor cases (70%).[1]

Causes

Differentiating Krukenberg tumor from other Diseases

  • Krukenberg tumor must be differentiated from:[1]

Epidemiology and Demographics

Incidence

  • The incidence of Krukenberg tumor is estimated to be approximately 0.16 per 100,000 individuals.[3][4]

Age

  • Patients of all age groups may develop Krukenberg tumor.
  • Krukenberg tumor is more commonly observed among women in the fifth decade, with an average age of presentation at 45 years of age.

Risk Factors

Natural History, Complications and Prognosis

  • The majority of patients with Krukenberg tumor remain asymptomatic or have non-specific gastrointestinal symptoms.[1]
  • Early clinical features include abdominal pain and distension (from the large, bilateral ovarian masses).[1]
  • If left untreated, patients with Krukenberg tumor may progress to develop virilization from the excessive hormone production from the ovarian stroma.[5]
  • Common complications of Krukenberg tumors include ascites, virilization, and pseudo-Meig syndrome.[5][1]
  • Prognosis is generally poor, and the 5 ­year survival rate of patients with Krukenberg tumor is lower in patients in with a preoperative serum CA-125 levels greater than 75 U/mL when compared with patients with CA-125 levels less than 75 U/mL.[6] The median survival of patients is between 7 to 14 months.[5]

Diagnosis

Symptoms

  • Krukenberg tumor is usually asymptomatic.[1]
  • Symptoms of Krukenberg tumor may include the following:[1][2]

Physical Examination

  • Patients with Krukenberg tumor usually appear well in the early stages.
  • Physical examination may be remarkable for:[1][2]

Laboratory Findings

  • There are no specific laboratory findings associated with Krukenberg tumors.

Imaging Findings

X Ray

  • On x ray, Krukenberg tumor may present with the following findings:[4]

Ultrasound

  • On pelvic ultrasound, Krukenberg tumor is characterized by the following:[3][4]
    • Bilateral, solid ovarian masses with clear, well defined margins
    • An irregular hyper-echoic solid pattern and moth eaten like cyst formation is also considered a characteristic feature

CT

  • On CT, Krukenberg tumor is characterized by the following:[4][11]
    • Large, lobulated, and multicystic masses with soft-tissue components which are indistinguishable from primary ovarian cancers
    • Presence of a concurrent gastric or colic mural lesion

MRI

  • On pelvic MRI, Krukenberg tumor is characterized by the following:[4][12][13][14]
    • Bilateral complex masses with hypo-intense solid components (dense stromal reaction)
    • Internal hyperintensity (mucin) on T1 and T2 weighted MR images
    • Strong contrast enhancement is usually seen in the solid component or the wall of the intratumoral cyst

Other Diagnostic Studies

Immunohistochemistry

Serum CA-125

  • Serum concentrations of CA-125 may be helpful for:[1]
    • Post-operative follow-up of patients for evaluation of complete resection of the tumor
    • Follow-up of patients with a history of primary adenocarcinomas (particularly gastrointestinal) for early detection of ovarian metastasis

Treatment

Medical Therapy

  • Management of Krukenberg tumor is driven by the identification and treatment of the primary cancer.
  • Chemotherapy/radiation has no significant effect on the prognosis of patients with Krukenberg tumors.[1]

Surgery

  • Bilateral oophorectomy may only be performed for patients where the metastasis is localized to the ovaries.[7]
  • The significance of early detection of ovarian metastasis and the importance of monitoring serum CA-125 level may improve the prognosis.
  • Surgical resection may not be an option if the tumor has already metastasized to other sites.

Prevention

  • There are no preventive measures available for Krukenberg tumors.

Case Studies

Case #1

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 Al-Agha OM, Nicastri AD (2006). "An in-depth look at Krukenberg tumor: an overview.". Arch Pathol Lab Med. 130 (11): 1725–30. PMID 17076540. doi:10.1043/1543-2165(2006)130[1725:AILAKT]2.0.CO;2. 
  2. 2.0 2.1 2.2 2.3 2.4 Krukenberg tumor. Wikipedia. https://en.wikipedia.org/wiki/Krukenberg_tumor#cite_note-Young2006-4 Accessed on March 21, 2016.
  3. 3.0 3.1 3.2 Tellier F, Steibel J, Chabrier R, Blé FX, Tubaldo H, Rasata R; et al. (2012). "Sentinel lymph nodes fluorescence detection and imaging using Patent Blue V bound to human serum albumin.". Biomed Opt Express. 3 (9): 2306–16. PMC 3447570Freely accessible. PMID 23024922. doi:10.1364/BOE.3.002306. 
  4. 4.0 4.1 4.2 4.3 4.4 4.5 Krukenberg tumour. Radiopedia. Accessed on March 23, 2016.
  5. 5.0 5.1 5.2 5.3 5.4 Hornung M, Vogel P, Schubert T, Schlitt HJ, Bolder U (2008). "A case of virilization induced by a Krukenberg tumor from gastric cancer.". World J Surg Oncol. 6: 19. PMC 2275731Freely accessible. PMID 18279511. doi:10.1186/1477-7819-6-19. 
  6. 6.0 6.1 Khan M, Bhatti RP, Mukherjee S, Ali AM, Gilman AD, Mirrakhimov AE; et al. (2015). "A 26-year-old female with metastatic primary gastrointestinal malignancy presenting as menorrhagia.". J Gastrointest Oncol. 6 (2): E21–5. PMC 4311099Freely accessible. PMID 25830046. doi:10.3978/j.issn.2078-6891.2014.080. 
  7. 7.0 7.1 Kim WY, Kim TJ, Kim SE, Lee JW, Lee JH, Kim BG; et al. (2010). "The role of cytoreductive surgery for non-genital tract metastatic tumors to the ovaries.". Eur J Obstet Gynecol Reprod Biol. 149 (1): 97–101. PMID 20018420. doi:10.1016/j.ejogrb.2009.11.011. 
  8. Krukenberg tumor. Wikipedia. https://en.wikipedia.org/wiki/Krukenberg_tumor#/media/File:Krukenberg_tumor_-3.jpg. Accessed on March 23, 2016
  9. Ovarian cancer. Wikipedia. https://en.wikipedia.org/wiki/Ovarian_cancer#Genetics Accessed on March 23, 2016.
  10. 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 Image courtesy of Dr Hani Al Salam. Radiopaedia (original file ‘’here’’). Creative Commons BY-SA-NC
  11. Cho KC, Gold BM (1985). "Computed tomography of Krukenberg tumors.". AJR Am J Roentgenol. 145 (2): 285–8. PMID 2992252. doi:10.2214/ajr.145.2.285. 
  12. Jung SE, Lee JM, Rha SE, Byun JY, Jung JI, Hahn ST (2002). "CT and MR imaging of ovarian tumors with emphasis on differential diagnosis.". Radiographics. 22 (6): 1305–25. PMID 12432104. doi:10.1148/rg.226025033. 
  13. Ha HK, Baek SY, Kim SH, Kim HH, Chung EC, Yeon KM (1995). "Krukenberg's tumor of the ovary: MR imaging features.". AJR Am J Roentgenol. 164 (6): 1435–9. PMID 7754887. doi:10.2214/ajr.164.6.7754887. 
  14. Imaoka I, Wada A, Kaji Y, Hayashi T, Hayashi M, Matsuo M; et al. (2006). "Developing an MR imaging strategy for diagnosis of ovarian masses.". Radiographics. 26 (5): 1431–48. PMID 16973774. doi:10.1148/rg.265045206. 

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