"Metastasis," in Greek meaning "change of the state," was first coined in 1829 to describe the process by which a neoplasm colonizes a distant part of the organism. Although as many as 8% of patients have multiple primary malignancies (Altinok et al., 1999), only about 150 cases of tumor-to-tumor metastases have been described in the literature since Berent's original case report in 1902 (Petraki et al., 2003). However, the number of reports has risen in recent years, probably due to increased awareness of the phenomenon as well as the availability of a wider array of immunostains to discriminate between two neoplasms (Tally et al., 1988).
In cases of tumor-to-tumor metastasis, lung carcinomas are by far the most common "donor" tumor, whereas renal cell carcinomas are the most common "recipient" (Petraki et al., 2003). In fact, up to 15% of renal cell carcinomas from patients with another malignancy may harbor a metastasis from that other tumor, especially in cases where the other tumor is widely disseminated (Sella and Ro, 1987). Even though breast carcinomas are also common donors, only two cases of breast carcinoma metastasizing to renal cell carcinoma have been described to date (Gore and Barr, 1958; Sella and Ro, 1987). Among intracranial neoplasms, meningiomas are the most likely to receive a metastasis from another neoplasm (Tally et al., 1988; Bhargava et al., 1999; Han et al., 2000). A wide array of donor and recipient tumors has been identified, so an open mind is essential in detecting these cases. This can be difficult, especially in cytologic preparations (Khurana and Powers, 1997).
Tumor-to-tumor metastasis must be differentiated from a collision tumor, which is strictly defined as two adjacent neoplasms invading each other. Unfortunately the two terms have often been used interchangeably in the literature. To clarify the issue, in 1968 Campbell et al. developed 4 criteria for tumor-to-tumor metastasis: 1.) at least 2 primary tumors must be present; 2.) the recipient tumor must be a true neoplasm; 3.) the metastasis has to demonstrate real growth in the recipient tumor, not simply contiguous invasion or nonadherent tumor emboli; 4.) metastases into lymphoid tissue involved by hematopoietic neoplasms do not count.
In general, aggressive epithelial neoplasms are the donors, whereas benign or low-grade malignant neoplasms are the recipients. But because relatively few cases of tumor-to-tumor metastases have been reported, only theories exist as to why it happens, and why certain tumors and locations are more likely to be donors or recipients. One is that the probability of being a recipient or donor is dependent on so-called "mechanical" issues. These include high blood flow, tumor vascularity, and anatomic location (Ewing, 1928). For example, since 25% of the blood minute volume flow passes through the kidneys, and since RCCs tend to be highly vascular tumors, it stands to reason that metastatic cells from another primary tumor would be more likely to colonize a coexistent RCC (Singh et al., 1984). A second theory is that circulating tumor cells prefer to colonize tissues that have a more favorable biochemical microenvironment (Paget, 1889). Thus, aggressive tumors are more likely to be donors than recipients because the anaerobic, nutrient-depleted microenvironment in high-grade tumors discourages colonization by other tumor cells. Slow-growing tumors, like many RCCs and meningiomas, generally have aerobic microenvironments. Furthermore, RCCs and meningiomas usually have abundant lipids, which are useful sources of energy for metastatic cells (Gore and Barr, 1958; Sella and Ro, 1987). A third explanation why slow-growing tumors are more likely to be recipients is that because they are slow-growing, they simply have more time to "catch" cells from another tumor. Any of these reasons would explain why other common recipients include pituitary adenomas and thyroid neoplasms, whereas lung carcinoma, breast carcinoma, and melanoma are the most common donors (Petraki et al., 2003). Of note, RCCs are distinct in that they are common donors and recipients (Sella and Ro, 1987).
In summary, this is a case of conventional renal cell carcinoma containing metastatic breast ductal carcinoma. From a clinical standpoint, the tumors are staged independently.
Contributed by Craig Horbinski, MD, PhD and Federico Monzon-Bordonaba, MD