Almost imperceptible malignant cells (dark nuclei in small clusters) are identified singly or as short cords blend into the spindled ovarian stroma.
Small gland-like cluster of cells without significant nuclear enlargement or atypia are seen.
Again, small cells with inconspicuous nuclei, but closer inspection reveals their signet ring morphology with cytoplasmic vacuoles and eccentric nuclei.
The malignant cells blend in with the normal stroma and do not elicit a desmoplastic response.
A Krukenberg tumor is type of metastatic adenocarcinoma to the ovary consisting of signet ring cells. The primary tumor is usually located in the stomach, however, other sites such as appendix, colon, breast and gallbladder can also give rise to Krukenberg tumors.
Microscopically, the trademark feature of signet ring carcinoma is barely detectable single malignant cells percolating through the stroma. Understandably, missing a signet ring carcinoma is a significant source of anxiety among surgical pathologists. The lesional cells can also form short cords, variably sized nests or scattered tubules.
The classic signet ring cell is a cell containing a large intracytoplasmic mucin globule, which pushes the hyperchromatic nuclei to the periphery thus creating the look of a signet ring as seen in profile. The stroma is usually hypercellular, but may also be focally edematous, hypocellular and harbor mucin pools. Malignant cells are frequently found in the ovarian hilar lymphatics. In situations when the malignant cells are difficult to detect, stains for neutral mucins (PAS or mucicarmine), cytokeratin 7 and epithelial membrane antigen may be helpful.
A primary ovarian Krukenberg tumor is a disputed entity. Only when a patient survives long-term after resection of an ovarian Krukenberg tumor OR no primary tumor can be identified during autopsy may this diagnosis be considered.1
Rare in the United States, but much more common in countries with a high incidence of gastric cancer such as Japan. Patients tend to be younger than expected for a metastatic carcinoma.
In a study of 120 Krukenberg tumors, the patients ranged from 13 to 84 years (average, 45 years) with 43% of them under 40 years (Kiyokawa); two-thirds arose from the stomach.3
The primary tumor in the stomach may escape detection as signet ring carcinomas are notorious for their camouflage. Metastasis can occur even if only intramucosal gastric carcinoma is identified due to early penetration of lymphatics. The tumors are bilateral in 60-70% of cases. The cut surface tends to be fleshy, firm and tan. Focal areas of necrosis and hemorrhage are common.
Poor prognosis. Worse if the gastric primary is identified after recognition of Krukenberg tumor.
♥ A Krukenberg tumor is a term for metastatic adenocarcinoma to the ovary consisting of signet ring cells. Usually arises from the stomach, but the appendix, colon or breast may also be the primary site.
♥ Histologically, sneaky signet rings infiltrate the ovarian stroma singly or in clusters -- and might be easily missed.
1 Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd Ed. Philadelphia, PA: Elsevier; 2007: 618-9.
2 Mills SE, ed. Sternberg's Diagnostic Surgical Pathology.4th Ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004: 2623-4.
Kiyokawa T, Young RH, Scully RE. Krukenberg tumors of the ovary: a clinicopathologic analysis of 120 cases with emphasis on their variable pathologic manifestations. Am J Surg Pathol. 2006 Mar;30(3):277-99.
McCluggage WG, Young RH. Primary ovarian mucinous tumors with signet ring cells: report of 3 cases with discussion of so-called primary Krukenberg tumor. Am J Surg Pathol. 2008 Sep;32(9): 1373-9.