Table of Contents
Definition / general | Terminology | Epidemiology | Pathophysiology | Clinical features | Laboratory | Radiology description | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Differential diagnosisCite this page: Parra-Herran C. Colorectal adenocarcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumorcolorectaladeno.html. Accessed January 25th, 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
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
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
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+