From Krukenberg to today: the ever present problems posed by metastatic tumors in the ovary. Part II.

Advances in Anatomic Pathology. 14(3):149-177, May 2007. [Link]

Young RH.

James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.


This is the second of a two-part consideration of metastatic tumors to the ovary. Here, the matter is considered in 16 categories, largely site-specific.

The first tumor discussed is gastric carcinoma of intestinal-type whose ovarian manifestations have been the subject of a recent paper which emphasized its differences from the Krukenberg tumor. Coverage of intestinal adenocarcinoma emphasizes the landmark 1987 paper of RH Lash and WR Hart. The section on pancreatic neoplasms reemphasizes the problems caused by metastatic ductal carcinoma, considered primarily in Part I, and discusses less common issues such as spread of neuroendocrine and acinar cell carcinomas. The limited information on spread of tumors of the gallbladder and extrahepatic bile ducts is then reviewed before more detailed consideration of hepatic neoplasms, prompted by recent contributions on hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the latter based on significant experience with this problem in Thailand. The section
on appendiceal neoplasms highlights ovarian spread of diverse tumors ranging from typical intestinal-type adenocarcinoma to signet-ring cell carcinomas with various patterns which in the ovary may prompt diagnoses such as a goblet cell (mucinous) carcinoid tumor, but whose ovarian features place them in the category of a Krukenberg tumor.

The diverse problems in differential diagnosis of carcinoid tumor (provoked by nested, acinar, and other patterns, including folliclelike spaces) are then reviewed. The section on breast cancer emphasizes that, although usually a manifestation of late stage disease and often not bulky in the ovaries, metastatic breast cancer may form large masses which can represent the clinical presentation. That patients with breast cancer have an increased risk of primary ovarian cancer and that the latter is more common than secondary spread of breast cancer is noted. The section on lung tumors largely reflects information in a recent paper that small cell carcinoma and adenocarcinoma are
the lung cancers that spread to the ovary most commonly. The extremely broad differential diagnosis posed by metastatic malignant melanoma ranging from that of an oxyphilic tumor, to a small cell tumor, to a follicle-forming neoplasm, is then considered. The sections on renal cell carcinoma and other urinary tract neoplasms emphasize the differential diagnosis of metastatic clear cell carcinoma and primary clear cell carcinoma, an issue usually resolvable by an awareness of the various features of the ovarian variant, rarely or never seen in the renal variant. The section on metastatic sarcomas discusses endometrial stromal sarcomas, gastrointestinal stromal neoplasms, and miscellaneous other sarcomas. The endometrial stromal tumors are problematic largely because the history of a primary tumor may be remote, in the ovaries the typical growth and vascular pattern of endometrial stromal neoplasms is not always conspicuous, and some endometrial stromal sarcomas in the ovary show sex cordlike patterns of growth.
Recent information has indicated that gastrointestinal stromal tumors may rarely have significant ovarian manifestations and if the primary neoplasm is overlooked, the ovarian tumor may be misdiagnosed, usually as an ovarian fibromatous tumor, but potentially as another primary neoplasm. The sections on ovarian spread of uterine carcinomas emphasize the problems owing to cervical adenocarcinomas, which have a greater tendency to involve the ovaries than squamous cell carcinomas and can simulate primary mucinous or endometrioid cancers. The final neoplasms considered are malignant mesothelioma and the desmoplastic small round cell tumor.

The microscopic features of malignant mesothelioma are so different from those of primary ovarian carcinoma in most instances that the diagnosis should be readily established on routine microscopic evaluation. The differential diagnosis of the desmoplastic small round cell tumor is more complex because of the greater overlap with the many other small cell malignant tumors that
may involve the ovaries primarily or secondarily. Nonetheless, differences exist in most cases and awareness of the entity should lead to consideration of the desmoplastic neoplasm, particularly in a young female.

In this area, as in a number of others considered in the review, immunohistochemistry may play a significant, sometimes crucial, role. However, as pointed out in brief concluding remarks, despite the aid of that modality, as in surgical pathology overall, careful consideration of the clinical background, distribution of disease, gross characteristics and spectrum of routine microscopic findings, will lead to the correct diagnosis in the majority of cases and at the very least lead to formulation of a considered differential diagnosis such that use of special techniques may be judicious and those results placed in context of the time-honored clinical and pathologic features.