Colorectal adenocarcinoma

Ovary

Metastases to ovary

Author: Carlos Parra-Herran, M.D.

Topic Completed: 1 June 2016

Minor changes: 10 March 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Colorectal adenocarcinoma [title]

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Table of Contents

Cite this page: Parra-Herran C. Colorectal adenocarcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumorcolorectaladeno.html. Accessed August 6th, 2020.

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

Terminology

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)

Epidemiology

The rate of secondary (metastatic) ovarian malignancies varies from 6 - 22% (Pathol Int 2005;55:231)
Of these, between 10 and 33% are of colorectal origin (World J Gastrointest Surg 2010;2:109)
1.2 - 14% of women with intestinal cancer will develop ovarian metastases (World J Gastrointest Surg 2010;2:109)

Pathophysiology

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)

Laboratory

Elevated CA125 levels (> 100 U/mL) are common, which may be useful to distinguish metastatic from primary ovarian mucinous carcinomas (Gynecol Obstet Invest 2011;72:196)
Elevated CEA levels (> 5 ng/mL) and CA19-9 levels (> 37 U/mL) are seen in a minority of cases (Gynecol Obstet Invest 2011;72:196)

Radiology description

Bilaterality ranges from 18 - 80% (Am J Surg Pathol 2006;30:177, Ultrasound Obstet Gynecol 2012;39:581, J Clin Pathol;65:585)
On imaging, the ovarian mass can be cystic, solid or a mixture
Surface involvement and necrosis are common
A smooth margin is seen in most lesions (92%), compared to primary ovarian tumors (45%)

Treatment

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
- They lack specificity since they are frequently positive in primary ovarian tumors
- SATB2 has been recently described as a more specific marker of colorectal origin (Int J Gynecol Pathol 2016;35:191, Ann Diagn Pathol 2015;19:249, Am J Surg Pathol 2016;40:419)
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)

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+