Our discussion highlights the uniqueness of bladder cancer metastasizing to the heart and explores the rare subtype of PUC. Bladder cancer is the fourth most common cancer in men in the United States [4
]. Normal patterns of metastasis typically follow a predictive pattern, first involving regional and juxtaregional lymph nodes, then liver, lungs, bones, and less commonly intestine, adrenal glands and kidneys [5
]. Most patients (69%) with metastatic bladder cancer have more than one organ involved [6
]. Cardiac metastases are much less common, with the first case reported in 1967 [7
]. At the time of this publication we are aware of only three other reported instances of isolated cardiac metastasis from urothelial cell carcinoma [1
Metastases to the heart and pericardium are incidentally discovered at autopsy in 10%–12% of patients with any type of malignancy [8
]. Primary tumors most likely to have cardiac metastasis found at autopsy include pleural mesotheliomas (48.4%), melanomas (27.8%), lung adenocarcinomas (21%), and undifferentiated carcinomas (19.5%) [9
]. It is very rare for malignancies to have solitary cardiac metastasis, with post-mortem studies finding rates of only 0.015%.
PUC is a rare and only recently described type of bladder cancer, with the first reported case in 1991 [10
]. It is estimated to make up less than three percent of all invasive bladder carcinomas [11
]. Although it is still a relatively new entity, data thus far has demonstrated that PUC is an aggressive tumor with extensive local growth and poor prognosis [12
The histopathology of PUC is characterized by invasive discohesive growth of plasmacytoid cells with eccentric nuclei. The normal immunohistochemical staining pattern for urothelial carcinomas is variable. Cytokeratin (CK) 7 staining occurs in the majority of these tumors; whereas as the CK20 expression varies from 15% to 97% depending on the study [13
]. PUC cells stain with CK, epithelial membrane antigen, GATA binding protein 3 (endothelial transcription factor 3), cluster of differentiation (CD) 15, CD138, protein 53 (p53), and protein 16 (p16) [14
A review of hematoxylin and eosin (H&E) stained sections of the biopsied primary tumor demonstrated an invasive urothelial carcinoma with discohesive epithelial cells and plasmacytoid features (Figure
). Subsequent immunohistochemical staining demonstrated positive cytoplasmic staining for pankeratin anion exchanger 1 and 3 (AE1/AE3, not shown), high molecular weight keratin (HMWK), CK7, and positive cell surface staining for CD138. All of the tumor cells had this staining pattern. The same cells were seen in the cardiac biopsy (Figure
) along with a prominent desmoplastic response not seen in the primary tumor. Immunohistochemical staining of the cardiac biopsy demonstrated positive staining for AE1/AE3, HMWK, CK7, and CD138. Although not performed on the primary tumor, the metastatic cells lacked staining for CK20, muscle-specific actin (HHF-35), myogenin, desmin, calretinin, the monoclonal antibody D2-40, Wilm’s tumor gene (WT-1), Melan-A, protein S-100, Human Melanoma Black (HMB-45), and CD45.
In general, the differential diagnosis for a CK7 positive and CK20 negative tumors include urothelial carcinoma, breast carcinoma, ovarian serous carcinoma, mesothelioma and prostatic carcinoma. In this case, the differential diagnosis is narrowed to urothelial carcinoma, mesothelioma and prostatic carcinoma. There was no clinical or radiographic evidence of mesothelioma, nor was there positive staining of the metastatic tumor for the mesothelial markers calretinin, WT-1, and D2-40. High molecular weight cytokeratin is highly sensitive marker for urothelial carcinomas and helps distinguish it from prostate carcinoma which lacks HMWK expression.
Cardiac magnetic resonance imaging was conducted to further image the myocardium to obtain information regarding the histopathologic composition of the tumor as well as to evaluate for any adverse hemodynamic effects. Cardiac MRI is superior for assessment of tumor morphology to assist with mass characterization. While hybrid PET/CT has been used for imaging of solid organs, this has not been widely used for cardiac imaging [17
Metastases from PUC have been reported in adjacent pelvic structures, bone, and peritoneum. [12
]. In a review of the literature, we have not identified any cases of isolated or non-isolated cardiac metastasis from this subtype of UCC. It is unknown why there have not been any other documented cases of metastasis to the heart, however a possible explanation may be that this tumor is usually spread via direct extension into surrounding structures rather than hematogenously.
PUC is often discovered at a late stage, which contributes to its poor prognosis. Our patient had a superficial PUC that did not invade the muscularis propria of his bladder wall. Conservative treatment was chosen for the patient based on these findings. Despite removal of any identifiable whether the initial biopsy report underestimated the staging, or whether tissue had already seeded the heart. Whole body PET suggested that the PUC did not persist in his bladder and had not metastasized to any other sites. Such findings point to the need for more aggressive interventions and close follow-up for patients with the plasmacytoid variant of UCC, regardless of the degree of tumor infiltration.