Tumor-to-tumor metastasis is a rare phenomenon. The first description of a tumor metastasizing to another distinct tumor was made in 1902 by Bernet. Since then, ∼200 cases were described. The most common donor tumor is lung cancer 1. Recipient tumors may be malignant or benign. Among the malignant tumors, renal cell carcinoma is the most frequent recipient 2. The most common nonmalignant recipient tumor is meningioma 3. In this report, we describe a case of colorectal adenocarcinoma that metastasized to an ovarian cystadenofibroma.
An 80-yr-old woman visited our hospital for evaluation of mild hematochezia. Colonoscopy revealed an ulcerated mass in the rectosigmoid colon, located 16 cm from the anal verge. Histologic examination of biopsies from the mass showed moderately differentiated adenocarcinoma. Nine years before her admission, the woman was diagnosed with a right ovarian cyst detected in routine ultrasonographic imaging studies. The cyst measured 10×8 cm with no evidence of solid areas, papillary structures, or septations, and hence it was interpreted as an incidental benign ovarian cyst. The patient underwent uneventful routine gynecologic follow-ups since its detection. Before her scheduled colectomy procedure, a CT scan was performed and showed no evidence for distant metastatic disease and an unremarkable right ovarian cyst. Nevertheless, as large ovarian cysts in an elderly patient may undergo malignant transformation, the gynecologists recommended performing prophylactic bilateral salpingo-oophorectomy in addition to colectomy.
On gross examination, the rectosigmoid colon specimen, revealed a centrally ulcerated mass with raised borders, measuring 4.5 cm in greatest dimension. Microscopic examination showed G2: moderately differentiated adenocarcinoma, extending into the subserosal adipose tissue of the peritonealized mesorectum. No macroscopic perforation was identified. In addition, 10 of 22 regional lymph nodes (10/22) were involved by metastasis. Thus, the tumor in the rectosigmoid colon was consistent with the pTNM stage pT3N2b. The cyst in the right ovary, measuring 10 cm on greatest dimension, had a serous fluid content. The inner and outer surfaces were smooth and unremarkable. Microscopically, the ovarian cyst was diagnosed as serous cystadenofibroma. In one of the samples obtained from the cyst wall, a 2.5 mm focus of infiltrating, irregular glandular structures in a desmoplastic stroma was seen. The cells were polygonal with eosinophilic cytoplasm, and few of them showed intracellular mucin production and “goblet-cell” formation. These cells showed a centrally located nucleus, with moderate pleomorphism, atypia, and prominent nucleoi. These histologic features are compatible with mucin-producing adenocarcinoma (Fig. 1A). Immunohistochemical studies showed that the adenocarcinoma was diffusely positive for CDX-2, Cytokeratin 20, and carcinogenic embryonic antigen (Figs. 1B–D), and it was negative for PAX-8, Cytokeratin 7, and estrogen receptor. In contrast, the serous epithelial lining of the cystadenofibroma showed opposite immunoexpression. These findings confirm the diagnosis of metastatic colorectal adenocarcinoma to an ovarian cystadenofibroma, T3N2bM1 upstaging. The non-neoplastic ovarian and tubal tissues were unremarkable, grossly and microscopically.
In 1968, 4 criteria were described by Campbell et al. 4 for the diagnosis of tumor-to-tumor metastasis: (1) the presence of 2 or more distinct primary tumors; (2) the recipient tumor must be a true neoplasm; (3) the metastatic neoplasm is a true metastasis with established growth in the recipient tumor and not the result of embolization or contiguous growth; (4) exclusion of metastasis to lymphatic tissue already involved by lymphoreticular tumors.
In the present case, 2 distinct tumors were present (colorectal adenocarcinoma and ovarian cystadenofibroma). The ovarian cystadenofibroma was a true neoplasm, and there was no contiguous growth and no adhesions between the 2 tumors. By these criteria, this case is indeed a tumor-to-tumor metastasis. We were able to find 13 reported cases of tumor-to-tumor metastasis to the ovary. These cases are summarized in Table 1. None of the reported cases was associated with colorectal cancer. Breast cancer was the most common donor tumor associated with 7 cases 5,7,10–12. Two cases involved lung cancer 6,13, and 2 cases involved uterine cervical cancer 9,15. The remaining 2 cases involved gastric cancer 14 and carcinoid of the small intestine 8. To the best of our knowledge, this is the first report of tumor-to-tumor metastasis, with colorectal cancer metastasizing into an ovarian tumor.
Metastasis to normal ovaries is not uncommon and occurs mostly from tumors of the endometrium, breast, and the gastrointestinal tract. Nevertheless, only few cases of these metastases are detected within primary ovarian tumors. The tendency of tumor-to-tumor metastasis to appear more frequently in specific tumors, such as renal cell carcinoma or meningioma, is still unexplained. One of the main mechanisms proposed to explain this phenomenon is the “seed and soil” theory 16. According to this theory, tumor develops when provided a fertile environment (the soil) that enables the tumor cells (the seed) to proliferate. In renal cell carcinomas, the rich vascularity and the high content of glycogen and lipids are believed to be the soil that attracts metastatic tumors cells. Meningiomas are also known to have significant hypervascularity 17. In ∼50% of ovarian cystadenofibromas, vascularization is detected by Doppler sonography 18. This increased blood flow in the cysts’ walls could be the “soil” for metastatic tumor cells.
Tumor-to-tumor metastasis is being described in different types of tumors and in increasing amount of cases. Being aware of this phenomenon is important, as it affects disease stage and treatment approach. In addition, cases of tumor-to-tumor metastasis can help us understand the unique environmental conditions that promote metastatic growth. This, in turn, might lead to the development of antimetastasis therapy. When 2 separate tumors from the same patient are resected, the possibility of tumor-to-tumor metastasis should be considered, and thorough pathologic examination of both tumors is recommended, even if one of them is clinically and radiologically benign.
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