Metastases to ovary

Colorectal adenocarcinoma

Topic Completed: 1 June 2016

Minor changes: 21 October 2020

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Colorectal adenocarcinoma [title]

Carlos Parra-Herran, M.D.
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Cite this page: Parra-Herran C. Colorectal adenocarcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumorcolorectaladeno.html. Accessed October 21st, 2021.
Definition / general
  • Secondary ovarian involvement by colorectal adenocarcinoma is, by definition, evidence of advanced tumor stage (pM1)
  • Most colorectal tumors with ovarian involvement originate in the rectosigmoid colon (Rev Gastroenterol Mex 1994;59:290)
  • There is significant overlap of clinical, radiologic and pathologic features between primary and metastatic ovarian adenocarcinoma
  • In the workup of mucinous or endometrioid-like ovarian neoplasms, a secondary malignancy should always be excluded pathologically or clinically
  • Although commonly used to refer to all metastatic carcinoma involving the ovary, Krukenberg tumor strictly refers to adenocarcinoma with signet ring cell differentiation, most of which (76%) arise from the stomach (J Clin Pathol;65:585)
  • Ovarian involvement appears to occur relatively early in tumor progression, given that many patients have ovarian metastases at cancer diagnosis
  • Spread to the ovaries can be hematogenous, lymphatic, transperitoneal or by direct extension (Rev Gastroenterol Mex 1994;59:290)
Clinical features
  • Median patient age is 51 years; 24% are 40 years or younger (World J Gastrointest Surg 2010;2:109)
  • Most patients manifest changes in bowel habits, rectal bleeding and bloating; constitutional symptoms are less frequent
  • Symptoms related to a pelvic mass include abdominal pain or discomfort, bowel obstruction, abnormal vaginal bleeding
  • Mean size of the metastatic lesion usually exceeds the size of the primary tumor
  • Most cases are stage pT3 (full thickness wall involvement) or pT4 (perforation of visceral peritoneum or direct invasion of adjacent structures); nodal involvement occurs in 87% (Am J Surg Pathol 2006;30:177)
Radiology description
  • Given the high frequency of ovarian involvement by colorectal cancer, and the high proportion of cases that are unsuspected before oophorectomy, preoperative investigation in a patient with an ovarian mass should include colonoscopy (Int J Gynecol Pathol 2008;27:182)
Gross description
  • Mass is frequently complex (solid and cystic) or purely solid
  • Purely cystic unilocular lesions are rare
  • Solid tumors have a multinodular appearance and extend to the ovarian / tumor surface
  • Tumor size ranges from 5 to 20 cm
  • Some authors have reported a predominant small size (< 10 cm) and bilateral ovarian involvement; algorithms based solely on laterality and size have been proposed to separate primary from secondary neoplasms with high accuracy (Am J Surg Pathol 2003;27:985, Am J Surg Pathol 2008;32:128)
  • There is reported evidence of significant overlap of such features: in a recent series, 42.8% and 85.7% of metastatic colorectal adenocarcinomas were unilateral and > 10 cm, respectively (Am J Surg Pathol 2006;30:177, Int J Gynecol Pathol 2016;35:191)
Microscopic (histologic) description
  • Metastatic colorectal adenocarcinoma to the ovary usually has a mucinous or a conventional glandular appearance
    • Mucinous carcinomas have intestinal (goblet cell) differentiation
    • Mucin extravasation and signet ring cell morphology can be seen
    • The term Krukenberg tumor should be reserved for adenocarcinoma involving the ovary with a signet ring cell component > 10% of the tumor volume, regardless of its site of origin (Adv Anat Pathol 2006;13:205)
    • Conventional tumor cytomorphology with mucin depletion mimics the architecture and cytoplasmic appearance of primary endometrioid tumor
    • Nuclear pleomorphism and hyperchromasia tend to be prominent, and exceed the expected for a primary ovarian tumor
    • Central glandular necrosis is also more typical of colorectal tumors, although is not entirely specific

  • Metastases frequently mimic the appearance of an ovarian mucinous neoplasm, and may have areas mimicking a borderline or even benign primary mucinous tumor

  • Several clinical and pathologic features have been described as indicative of secondary (metastatic) origin (Am J Surg Pathol 2003;27:281, J Clin Pathol 2012;65:591), including:
    • Bilaterality
    • Size less than 10 cm
    • Surface involvement
    • Infiltrative pattern of invasion
    • Presence of signet ring cells
    • Extensive lymphovascular space invasion
    • Mucin extravasation

  • If any of the above features is present, the possibility of a metastasis should be considered and prompt ancillary testing and clinical investigation
Microscopic (histologic) images

Contributed by Carlos Parra-Herran, M.D.





Positive stains
  • Immunohistochemistry is useful to distinguish primary ovarian tumors and GI metastases, but must be interpreted with caution, since there is significant overlap in expression (Int J Gynecol Pathol 2016;35:191)

  • CK20, CDX2 and MUC2 are sensitive markers of colorectal origin
  • Rates of expression in colorectal tumors are:
    • SATB2: 75 - 79% (vs 5% of primary ovarian mucinous tumors and 0% of primary ovarian endometrioid tumors)
    • CK20: 68 - 85% (vs 45% of primary ovarian tumors)
    • CDX2: 64 - 100% (vs 50% of primary ovarian tumors)
    • MUC2: 97% (vs 40% of primary ovarian tumors)
    • Beta-catenin: 51% (vs 5% of primary ovarian tumors)
    • CK7: 21% (vs 95% of primary ovarian tumors)
Negative stains
  • PAX8: 0% (vs 30 - 65% of primary ovarian mucinous tumors and 80% of primary ovarian endometrioid tumors)
  • ER: 0% (vs 30% of primary ovarian tumors)

Contributed by Carlos Parra-Herran, M.D.

An algorithm to determine origin using currently available markers

Differential diagnosis
  • Metastases from upper GI tract: CK7 positive, CK20/CDX2/SATB2 variable (mostly negative)
  • Metastases from cervix: p16 positive (strong, diffuse)
  • Primary ovarian neoplasm (benign, borderline or malignant): no suspicious features described above (bilaterality, surface involvement, signet ring cell morphology, etc), PAX8+
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