Very few reports of tumor-to-tumor metastasis are present in the English literature. The terms “tumor-to-tumor metastasis” and “collision tumor” have often been confused with one another, and used incorrectly in the literature. Collision tumor is defined as two neighboring neoplasms that invade one another. Tumor-to-tumor metastasis has proved more difficult to be defined, with several proposed similar criteria in order to be classified correctly. The criteria of Campbell et al. to define tumor-to-tumor metastasis are as follows . (1) more than one primary tumor must exist; (2) the recipient tumor is a true benign or malignant neoplasm; (3) the metastatic neoplasm is a true metastasis with established growth in the host tumor, not the result of contiguous growth (collision tumor) or embolization of tumor cells; (4) involvement by metastatic tumors of lymph nodes already involved by lymphoproliferative disease (lymphoreticular malignant tumors) is excluded. According to the literature, renal clear cell carcinoma is the most common tumor recipient of metastasis while lung carcinoma is the most common donor tumor [1, 2, 6]. Tumor-to-tumor metastasis is not as infrequent as previously thought and may be present in up to 15 percent of patients with simultaneous renal clear cell carcinoma and second neoplastic disease . Commonly, the donor tumor is an aggressive malignant tumor. On the other hand, the recipient tumor is usually a low-grade malignancy or benign neoplasm. It is extremely rare that an aggressive malignant tumor as the recipient tumor while a low-grade malignancy as the donor tumor. Only three cases of papillary thyroid carcinoma, a low-grade malignancy, metastasizing to a lung cancer, an aggressive malignant tumor, were reported [3–5]. There were more reports about lung cancer metastasizing to a thyroid tumor [7–10].
The tumor cells (forming the ‘seed’) are hematogenously disseminated in a widespread manner to different anatomic sites, but attain successful growth and propagation only under the favorable local microenvironments of specific organs or the recipient tumors (the ‘soil’). Renal clear cell carcinoma is the most common recipient tumor in tumor-to-tumor metastasis. This might be attributable to its increased vascularity. Biochemical properties of renal cell carcinoma, such as increased cytoplasmic lipid and glycogen of constituent cells, has also been proposed as contributing to this tumor being a favorable site for metastatic growth . The lung is one of the most frequent sites of metastasis for the extrathoracic cancers. However, lung carcinoma is one of the rarest recipients for tumor-to-tumor metastasis. Presence of different vascular structures between normal lung and lung cancer may be the possible reason for the different potential as a site of metastasis. Unlike normal lung, lung cancer doesn’t contain a rich network of small thin-walled blood vessels. The other possible explanation which we considered was that lung cancer is rapidly growing tumor therefore it cannot provide a suitable environment for the acceptance of metastasis. Regarding the reason for the relatively high incidence of lung cancer as a donor in tumor-to-tumor metastasis, the rich vascularity of lung carcinoma in association with the probable shedding of tumor cells during respiratory movement might increase the frequency of invasion into the pulmonary vein and subsequently into the general circulation. The tumor emboli from lung cancer have a better chance to reach all the body organs through the left-sided cardiac output than cancers of the other organs.
It is still unexplained whether tumor-to-tumor metastasis is merely of a chance occurrence or is a selective growth within the recipient tumor. In our case, a lung mass with metastatic papillary thyroid carcinoma was the first metastatic focus discovered during the post-operative follow-up of this patient. Our case showed that the metastatic papillary thyroid adenocarcinoma foci were not limited to the primary lung adenocarcinoma and multiple microscopic foci of thyroid papillary foci were observed in the surrounding normal lung tissue. Multi foci of metastases can also be seen both within the lung cancer and in the background lung tissue in the 3 reported cases of a lung cancer acting as the recipient of a donor of papillary thyroid carcinoma [3–5]. In addition, multiple spreading small lung adenocarcinoma can also be seen in the background lung tissue in our present case while the 3 reported cases didn’t show this. Papillary thyroid carcinoma is a slowly growing tumor. Disease-specific survival with distant metastases at 5 and 10 years was reported to be 65 and 45%, respectively . The metastatic foci of papillary thyroid carcinoma had probably already been there before lung primary adenocarcinoma occurred, and the metastases to lung cancer had occurred by chance.
The presence of a lung mass in a patient with a prior cancer can represent a clinically and/or pathologically diagnostic challenge. Some of these lung masses represent primary processes rather than metastatic deposits. The diagnosis of metastatic carcinoma to the lung by core biopsy, frozen section, and permanent sections can be easily misinterpreted as a primary tumor. The possibility of metastatic papillary thyroid carcinoma should always be considered when two different cell populations are identified, and specifically, one should be aware of in the presence of papillary component in a lung carcinoma. The diagnosis of metastatic papillary thyroid carcinoma mainly depends on the morphology of the nucleus and immunohistochemical expression. The papillary thyroid carcinoma is composed of cells with ground glass nuclei in the cells and colloid in the thyroid follicles, which are the important characteristics different from other carcinomas. Lepdic or adenocarcinoma in situ components in the surgical specimens can also help to differentiate primary lung adenocarinoma from other carcinomas. Thyroid Transcription Factor-1 is one of the immunohistochemical markers most commonly used to assist in the differential diagnosis of carcinomas of the lung and thyroid from other carcinomas. But it cannot differentiate between lung carcinoma and thyroid carcinoma. CK19, galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1) have been studied to distinguish between malignant and benign lesions of the thyroid gland. The diagnostic efficiency of CK19 for papillary thyroid carcinoma was slightly better than that of Gal-3 and HBME-1. The utilization of these markers combined with morphologic evaluation may be helpful in the differential diagnosis of papillary thyroid carcinoma and benign lesions [13, 14]. But they cannot distinguish metastatic papillary thyroid carcinoma from lung adenocarcinoma. Thyroglobulin is an antibody specially expressed in normal thyroid and thyroid carcinoma, which we can use in the differential diagnosis of lung carcinoma and thyroid carcinoma. Napsin A is an aspartic proteinase involved in the maturation of surfactant protein B. It is detected in the cytoplasm of type 2 pneumocytes and alveolar macrophages and is a putative marker for lung adenocarcinomas. It can also help to differentiate lung adenocarcinoma from metastatic papillary thyroid carcinoma . Recently, microarray based gene expression profiling has found increasing use, particularly in the most difficult cases. Gene expression profiling provides correct primary site identification in a higher percentage, of metastatic cases than immnunohistochemistry-guided methods (90% vs. 64%), and uses less tissue . In our present case, the morphology and immunohistochemical expression of the two components were typical. It was a rare case, but not difficult for pathologist, so gene expression profiling is not necessary.