Ovary tumor
Metastases to ovary
Appendiceal neoplasms

Author: Carlos Parra-Herran, M.D. (see Authors page)

Revised: 7 June 2016, last major update June 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Appendiceal neoplasms [title]

Cite this page: Appendiceal neoplasms. PathologyOutlines.com website. http://pathologyoutlines.com/topic/ovarytumorappendiceal.html. Accessed May 29th, 2017.
Definition / general
  • Mucinous neoplastic proliferations of the cecal appendix commonly manifest with signs of extra-appendiceal spread, particularly in the form of pseudomyxoma peritonei
  • Involvement of other organs such as the ovary may be the first manifestation of the disease
  • Current evidence supports that, in the context of pseudomyxoma peritonei, an ovarian mucinous tumor should be regarded as appendiceal in origin, with the exception of a mucinous tumor arising in a mature teratoma (Am J Surg Pathol 1991;15:415, Int J Gynecol Pathol 1997;16:1)
Terminology
  • Pseudomyxoma peritonei is a clinicopathologic syndrome characterized by mucinous ascites
  • Intra-abdominal mucin is abundant and can be admixed with neoplastic mucinous epithelium (Am Soc Clin Oncol Educ Book 2013;221)
  • Although commonly used to refer to all metastatic carcinomas involving the ovary, the term Krukenberg tumor strictly refers to adenocarcinomas with signet-ring cell differentiation, of which most (76%) arise from the stomach (J Clin Pathol 2012;65:585)
Epidemiology
  • Primary appendiceal tumors are found in < 2% of surgically removed appendices (Arch Pathol Lab Med 2011;135:1261)
  • 28 - 37% of appendiceal tumors not associated with pseudomyxoma peritoneii present with ovarian metastases (Gynecol Oncol 2014;133:155)
  • Among patients with ovarian mucinous tumors showing borderline features, only about 2% have a documented primary appendiceal malignancy
  • Despite this low incidence, there is significant overlap of clinical, radiologic and pathologic features between primary and metastatic ovarian adenocarcinoma; in the work-up of a mucinous or endometrioid-like ovarian neoplasm, a secondary malignancy should always be considered pathologically or clinically
  • Pseudomyxoma peritonei is 2 - 3 times more common in women than in men
Pathophysiology
  • Spread to the ovaries can be hematogenous, lymphatic, transperitoneal or by direct extension (Rev Gastroenterol Mex 1994;59:290)
  • The pathogenesis of pseudomyxoma peritonei is still unknown; current theories postulate that the mucin is produced by very low quantities (sometimes undetectable) of neoplastic intestinal-type epithelium, which colonizes the peritoneal cavity presumably after appendiceal tumor rupture
Clinical features
  • Patients with metastatic appendiceal adenocarcinoma involving the ovary have a poor prognosis
  • Patients with a low grade appendiceal mucinous neoplasm (LAMN) and pseudomyxoma peritonei has a protracted clinical course with multiple recurrences, progressive fibrous adhesions and complications such as fatal obstructive disease
Laboratory
  • Elevated CA-125 levels (> 100 U/mL) are common, which has been suggested as a useful feature 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
Radiology description
  • Bilaterality is seen in up to 83.3% of cases
  • On imaging, pseudomyxoma peritonei is suspected if there is irregularly localized or loculated fluid with scalloped appearance within the peritoneal cavity
  • The ovarian mass can be cystic, solid or a mixture
Gross description
  • Ovarian 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
  • Cut surface reveals mucinous contents in cystic areas and a soft, glistening appearance of solid areas, sometimes with easily expressed mucinous material from it
Gross images

Images hosted on other servers:

Krukenberg tumor of appendiceal origin

Microscopic (histologic) description
  • Low grade appendiceal mucinous neoplasms (LAMN) have bland cytomorphology and mimic benign and borderline ovarian mucinous tumors
  • LAMN involving the ovary display certain distinctive microscopic features (Int J Gynecol Pathol 2014;33:1):
    • Bilaterality
    • Tall mucinous cells with indistinct apical borders and lack of cellular stratification
    • Elongated glands with shallow epithelial invaginations (scalloping)
    • Subepithelial clefts
  • These characteristics, however, can also be seen in up to 38.8% of ovarian mucinous borderline tumors
  • Appendiceal adenocarcinomas can have a mucinous or a conventional (mucin-depleted) 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 to adenocarcinomas 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 tumors; however, nuclear pleomorphism and hyperchromasia tend to be prominent, and exceed that expected for a primary ovarian tumor
    • Central glandular necrosis is also more typical of intestinal tumors, although is not entirely specific
  • 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

Images hosted on PathOut servers:

Contributed by Carlos Parra-Herran, M.D.

Positive stains
  • Immunohistochemistry is a reliable tool in the distinction between primary ovarian tumors and metastases from appendiceal origin
  • SATB2 is a sensitive and specific marker of colorectal epithelium
    • Also positive in appendiceal epithelium
    • This marker has shown 93.8% sensitivity and 97.5% specificity in determining appendiceal origin (Histopathol 2016;68:977)
  • CK20, CDX2 and MUC2 are also optimal markers of appendiceal origin; although they are frequently expressed in primary ovarian tumors, such expression is usually patchy / focal
  • Diffuse and strong expression for CK20, CDX2 and MUC2 has 90%, 87.5% and 95% specificity for appendiceal origin
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)
Differential diagnosis
  • Low grade mucinous neoplasm or mucinous carcinoma with pseudomyxoma peritonei arising in a mature cystic teratoma (Am J Surg Pathol 2007;31:854)
  • Metastases from cervix: p16 positive (strong, diffuse)
  • Metastases from colon and rectum: mass located in the large intestine, normal appendix (colorectal and appendiceal tumors have a similar IHC profile)
  • Metastases from upper GI tract: CK7 positive, CK20 / CDX2 / SATB2 variable (mostly negative)
  • Primary ovarian neoplasm (benign, borderline or malignant): absence of suspicious features described above (bilaterality, surface involvement, signet-ring cell morphology, etc), SATB2 negative, CK20 / CDX2 / MUC2 negative or patchy, PAX8 positive