Urothelial carcinoma metastases impacting the CNS: A 20-year retrospective series

Brain metastases are the most common adult brain tumor, with the breast, lung, skin (melanoma) being the most frequent primary malignancies to spread to brain [22]. Certain types of systemic malignancies are well known for their CNS-impacting metastases to occur several years after the primary tumor, whereas for other types of tumors, the CNS-impacting lesion may be the first clinical presentation [5], [20], [22].

Our group has a longstanding interest in metastases impacting the CNS, either within brain parenchyma or vertebral bone with impingement on the spinal cord, often necessitating urgent neurosurgical intervention to decompress the spinal cord. We have previously published our experience with metastases from prostatic carcinoma [21] and thyroid carcinoma [10] to brain, spinal cord parenchyma, and adjacent bony vertebra and skull, including the latter since usually these bony metastases undergo resection by neurosurgeons. We found that the intervals between diagnosis of primary tumor and the metastasis from prostatic adenocarcinomas was extremely varied, ranging from 0 to 26 years [21]. Similarly, interval periods between primary diagnosis of thyroid carcinomas and the CNS-impacting metastasis for intraparenchymal brain and bony spine metastases were 6 months to >30 years and 0 to 10 years, respectively [10]. We have also encountered examples of unusual CNS metastases with exceedingly long intervals between primary and metastatic tumor, including a 33-year interval for alveolar soft part sarcoma [12], and a 32-year interval for a tibial adamantinoma [23]. Either presentation as the first sign of systemic malignancy or a very long interval between primary and metastatic CNS tumor may contribute to considerable diagnostic confusion for both the clinical team and the pathologist at the time of biopsy, especially in instances where there is limited availability of past medical history. Thus, the pathologist benefits from being aware of the biological aspects of metastatic CNS tumors.

In the current study, we direct our attention towards one of the least frequent types of tumors to spread to the brain, namely urothelial carcinoma. Primary urothelial carcinomas, also known as transitional cell carcinomas, can arise from anywhere along the urothelial tract, including bladder, ureters, urethra, calyces, and renal pelvis. CNS-impacting metastases from urothelial carcinoma are rare and in some studies have been associated with a poor prognosis [20], [22], [26]. However, there is a suggestion from the few prior reports in the literature that as treatment for urothelial carcinoma has improved over the last 20 years, the survival time post initial primary diagnosis has increased as well, which might increase the possibility of CNS metastasis [7].

Given the fact that only case reports and small series exist in the literature on this tumor type [7], [20], we investigated how many examples of CNS-impacting urothelial metastases we had encountered over the past 20 years, focusing on documenting intervals between primary and metastasis, as well as survival times post-CNS metastasis. We especially noted if any examples had been first presentations of the systemic primary, since the role of the pathologist in cancer diagnosis is particularly critical when the patient's first presentation of their systemic malignancy occurs within the brain in a patient not known to harbor a solid organ tumor.

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